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Adiponectin and leptin content in subcutaneous and visceral adipose tissues, lipolysis and adipocyte size distribution of mice with pharmacological ER stress. Mice were administered vehicle (C), tunicamycin (1 g/kg body weight) for 8 h (T8) or 24 h (T24), pioglitazone (15 mg/kg/day) for 20 days (P) or pioglitazone + tunicamycin 8 h (PT8), and pioglitazone + tunicamycin 24 h (PT24) to evaluate adiponectin multimeric distribution in serum, adiponectin and leptin content in adipose tissue (A), densitometric analysis of adiponectin in serum (B) and adipose tissues (C), adiponectin mRNA content in subcutaneous and visceral adipose tissue (D). Serum leptin content (E) and leptin protein abundance (F) and mRNA content (G) in subcutaneous and visceral adipose tissues. Circulating free fatty acids (H) and glycerol (I). Protein content of p-HSL (Ser660) and total HSL in adipose tissues (J) and densitometric analysis of p-HSL/HSL (K). Size frequency distribution of subcutaneous and visceral adipocytes (L). The band corresponding to the IgG light chain after coomassie blue membrane staining was used as a loading control in serum samples and GAPDH in adipose tissue samples. Error bars represent SEM. n = 8-10. Letters denote significant differences between groups, a > b > c > d (P < 0.05)
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Subcutaneous (SAT) and visceral (VAT) adipose tissues stores excess energy as triglycerides and synthesize adiponectin to prevent ectopic lipid accumulation and lipotoxicity. During obesity, an impairment in the capacity of SAT to store triglycerides and synthesize adiponectin is associated with increased free fatty acids (FFA) release, leading to...
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... is known that endoplasmic reticulum stress stimulates lipolysis in adipocytes. 34 To further investigate the effect of acute ER stress on SAT and VAT in lipolysis and its relative participation to circulating FFA we determined serum FFA and glycerol concentrations and adipose tissue hormone- sensitive lipase (HSL) phosphorylation in ser660. Circulating FFA and glycerol increased after tunicamycin administration in both control and pioglitazone-treated mice (Figures 3H and 3I). Total HSL protein content was higher in SAT than in VAT in all treatment conditions (Figures 3J and 3K). In SAT, HSL phosphorylation at Ser660 increased after 24 h of tunicamycin administration with respect to control. In mice treated with pioglitazone, p-HSL was also higher in tunicamycin-treated mice compared to those administered pioglitazone alone. In contrast to SAT, the phosphorylation of HSL in VAT was lower in mice administered tunicamycin for 24 h than those administered vehicle. Consistent to HSL phosphorylation, subcutaneous adipocytes were reduced in size after tunicamycin administration, whereas adipocytes from the visceral depot increased in size ( Figure 3L). These results indicate that increased circulating FFA are mainly the result of augmented lipolysis in SAT in response to acute ER stress. , and pioglitazone + tunicamycin 24 h (PT24) to evaluate adiponectin multimeric distribution in serum, adiponectin and leptin content in adipose tissue (A), densitometric analysis of adiponectin in serum (B) and adipose tissues (C), adiponectin mRNA content in subcutaneous and visceral adipose tissue (D). Serum leptin content (E) and leptin protein abundance (F) and mRNA content (G) in subcutaneous and visceral adipose tissues. Circulating free fatty acids (H) and glycerol (I). Protein content of p-HSL (Ser660) and total HSL in adipose tissues (J) and densitometric analysis of p-HSL/HSL (K). Size frequency distribution of subcutaneous and visceral adipocytes (L). The band corresponding to the IgG light chain after coomassie blue membrane staining was used as a loading control in serum samples and GAPDH in adipose tissue samples. Error bars represent SEM. n = 8-10. Letters denote significant differences between groups, a > b > c > d (P < ...
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... is known that endoplasmic reticulum stress stimulates lipolysis in adipocytes. 34 To further investigate the effect of acute ER stress on SAT and VAT in lipolysis and its relative participation to circulating FFA we determined serum FFA and glycerol concentrations and adipose tissue hormone- sensitive lipase (HSL) phosphorylation in ser660. Circulating FFA and glycerol increased after tunicamycin administration in both control and pioglitazone-treated mice (Figures 3H and 3I). Total HSL protein content was higher in SAT than in VAT in all treatment conditions (Figures 3J and 3K). In SAT, HSL phosphorylation at Ser660 increased after 24 h of tunicamycin administration with respect to control. In mice treated with pioglitazone, p-HSL was also higher in tunicamycin-treated mice compared to those administered pioglitazone alone. In contrast to SAT, the phosphorylation of HSL in VAT was lower in mice administered tunicamycin for 24 h than those administered vehicle. Consistent to HSL phosphorylation, subcutaneous adipocytes were reduced in size after tunicamycin administration, whereas adipocytes from the visceral depot increased in size ( Figure 3L). These results indicate that increased circulating FFA are mainly the result of augmented lipolysis in SAT in response to acute ER stress. , and pioglitazone + tunicamycin 24 h (PT24) to evaluate adiponectin multimeric distribution in serum, adiponectin and leptin content in adipose tissue (A), densitometric analysis of adiponectin in serum (B) and adipose tissues (C), adiponectin mRNA content in subcutaneous and visceral adipose tissue (D). Serum leptin content (E) and leptin protein abundance (F) and mRNA content (G) in subcutaneous and visceral adipose tissues. Circulating free fatty acids (H) and glycerol (I). Protein content of p-HSL (Ser660) and total HSL in adipose tissues (J) and densitometric analysis of p-HSL/HSL (K). Size frequency distribution of subcutaneous and visceral adipocytes (L). The band corresponding to the IgG light chain after coomassie blue membrane staining was used as a loading control in serum samples and GAPDH in adipose tissue samples. Error bars represent SEM. n = 8-10. Letters denote significant differences between groups, a > b > c > d (P < ...
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... is known that endoplasmic reticulum stress stimulates lipolysis in adipocytes. 34 To further investigate the effect of acute ER stress on SAT and VAT in lipolysis and its relative participation to circulating FFA we determined serum FFA and glycerol concentrations and adipose tissue hormone- sensitive lipase (HSL) phosphorylation in ser660. Circulating FFA and glycerol increased after tunicamycin administration in both control and pioglitazone-treated mice (Figures 3H and 3I). Total HSL protein content was higher in SAT than in VAT in all treatment conditions (Figures 3J and 3K). In SAT, HSL phosphorylation at Ser660 increased after 24 h of tunicamycin administration with respect to control. In mice treated with pioglitazone, p-HSL was also higher in tunicamycin-treated mice compared to those administered pioglitazone alone. In contrast to SAT, the phosphorylation of HSL in VAT was lower in mice administered tunicamycin for 24 h than those administered vehicle. Consistent to HSL phosphorylation, subcutaneous adipocytes were reduced in size after tunicamycin administration, whereas adipocytes from the visceral depot increased in size ( Figure 3L). These results indicate that increased circulating FFA are mainly the result of augmented lipolysis in SAT in response to acute ER stress. , and pioglitazone + tunicamycin 24 h (PT24) to evaluate adiponectin multimeric distribution in serum, adiponectin and leptin content in adipose tissue (A), densitometric analysis of adiponectin in serum (B) and adipose tissues (C), adiponectin mRNA content in subcutaneous and visceral adipose tissue (D). Serum leptin content (E) and leptin protein abundance (F) and mRNA content (G) in subcutaneous and visceral adipose tissues. Circulating free fatty acids (H) and glycerol (I). Protein content of p-HSL (Ser660) and total HSL in adipose tissues (J) and densitometric analysis of p-HSL/HSL (K). Size frequency distribution of subcutaneous and visceral adipocytes (L). The band corresponding to the IgG light chain after coomassie blue membrane staining was used as a loading control in serum samples and GAPDH in adipose tissue samples. Error bars represent SEM. n = 8-10. Letters denote significant differences between groups, a > b > c > d (P < ...
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... western blotting of mouse serum revealed that total and HMW adiponectin significantly increased after 8 h of tunicamycin administration but decreased after a 24 h tunicamycin challenge (Figures 3A and 3B). Pioglitazone significantly increased circulating adiponectin content with respect to control mice, but it was reduced after 24 h of tunicamycin administration. To evaluate the relative participa- tion of each adipose tissue depot in adiponectin synthesis, we measured adiponectin protein and mRNA abundance in SAT and VAT. Tunicamycin administration reduced adiponectin content in SAT, despite increased mRNA abundance. In contrast, adiponectin content in VAT was lower at 8 h of tunicamycin administration along with a reduction in mRNA content, but both protein abundance and mRNA content increased at 24 h to levels similar to that of the unstressed state ( Figures 3A, 3C, and 3D). Pioglitazone increased adiponectin content in both adipose tissue depots without a significant increase in its mRNA content. Induction of acute ER stress with tunicamycin decreased adiponectin protein content in both adipose tissue depots, however the reduction was more pronounced in SAT with respect to VAT ( Figures 3A, 3C, and 3D). To evaluate if leptin synthesis and secretion is also dependent on ER stress, we determined circulating leptin and leptin protein and mRNA abundance in adipose tissues. The circulating leptin concentration was not modified by acute ER stress as observed in mice administered with tunicamycin ( Figure 3E). However despite that 20 days of pioglitazone , and CHOP (D) and protein content of p-eIF2α, total eIF2α, p-JNK, and total JNK in adipose tissues (E), densitometric analysis of p-eIF2α/eIF2α (F) and p-JNK/JNK (G). Error bars represent SEM. n = 6-8. Letters denote significant differences between groups, a > b > c > d (P < 0.05) treatment increased serum leptin, it was significantly reduced after 24 h of tunicamycin challenge. Tunicamycin also reduced the leptin protein content in SAT, although the leptin gene expression was not reduced with respect to unstressed mice ( Figures 3A 3F, and 3G). In contrast, the increase in leptin protein and mRNA content in VAT in response to pioglitazone were not reduced after tunicamycin administration ( Figures 3A, 3F, and 3G). These results indicate that acute ER stress can impair the synthesis of secretory proteins such as adiponectin and leptin in SAT at a higher extent than in VAT, which associates with the circulating content of these ...
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... western blotting of mouse serum revealed that total and HMW adiponectin significantly increased after 8 h of tunicamycin administration but decreased after a 24 h tunicamycin challenge (Figures 3A and 3B). Pioglitazone significantly increased circulating adiponectin content with respect to control mice, but it was reduced after 24 h of tunicamycin administration. To evaluate the relative participa- tion of each adipose tissue depot in adiponectin synthesis, we measured adiponectin protein and mRNA abundance in SAT and VAT. Tunicamycin administration reduced adiponectin content in SAT, despite increased mRNA abundance. In contrast, adiponectin content in VAT was lower at 8 h of tunicamycin administration along with a reduction in mRNA content, but both protein abundance and mRNA content increased at 24 h to levels similar to that of the unstressed state ( Figures 3A, 3C, and 3D). Pioglitazone increased adiponectin content in both adipose tissue depots without a significant increase in its mRNA content. Induction of acute ER stress with tunicamycin decreased adiponectin protein content in both adipose tissue depots, however the reduction was more pronounced in SAT with respect to VAT ( Figures 3A, 3C, and 3D). To evaluate if leptin synthesis and secretion is also dependent on ER stress, we determined circulating leptin and leptin protein and mRNA abundance in adipose tissues. The circulating leptin concentration was not modified by acute ER stress as observed in mice administered with tunicamycin ( Figure 3E). However despite that 20 days of pioglitazone , and CHOP (D) and protein content of p-eIF2α, total eIF2α, p-JNK, and total JNK in adipose tissues (E), densitometric analysis of p-eIF2α/eIF2α (F) and p-JNK/JNK (G). Error bars represent SEM. n = 6-8. Letters denote significant differences between groups, a > b > c > d (P < 0.05) treatment increased serum leptin, it was significantly reduced after 24 h of tunicamycin challenge. Tunicamycin also reduced the leptin protein content in SAT, although the leptin gene expression was not reduced with respect to unstressed mice ( Figures 3A 3F, and 3G). In contrast, the increase in leptin protein and mRNA content in VAT in response to pioglitazone were not reduced after tunicamycin administration ( Figures 3A, 3F, and 3G). These results indicate that acute ER stress can impair the synthesis of secretory proteins such as adiponectin and leptin in SAT at a higher extent than in VAT, which associates with the circulating content of these ...
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... western blotting of mouse serum revealed that total and HMW adiponectin significantly increased after 8 h of tunicamycin administration but decreased after a 24 h tunicamycin challenge (Figures 3A and 3B). Pioglitazone significantly increased circulating adiponectin content with respect to control mice, but it was reduced after 24 h of tunicamycin administration. To evaluate the relative participa- tion of each adipose tissue depot in adiponectin synthesis, we measured adiponectin protein and mRNA abundance in SAT and VAT. Tunicamycin administration reduced adiponectin content in SAT, despite increased mRNA abundance. In contrast, adiponectin content in VAT was lower at 8 h of tunicamycin administration along with a reduction in mRNA content, but both protein abundance and mRNA content increased at 24 h to levels similar to that of the unstressed state ( Figures 3A, 3C, and 3D). Pioglitazone increased adiponectin content in both adipose tissue depots without a significant increase in its mRNA content. Induction of acute ER stress with tunicamycin decreased adiponectin protein content in both adipose tissue depots, however the reduction was more pronounced in SAT with respect to VAT ( Figures 3A, 3C, and 3D). To evaluate if leptin synthesis and secretion is also dependent on ER stress, we determined circulating leptin and leptin protein and mRNA abundance in adipose tissues. The circulating leptin concentration was not modified by acute ER stress as observed in mice administered with tunicamycin ( Figure 3E). However despite that 20 days of pioglitazone , and CHOP (D) and protein content of p-eIF2α, total eIF2α, p-JNK, and total JNK in adipose tissues (E), densitometric analysis of p-eIF2α/eIF2α (F) and p-JNK/JNK (G). Error bars represent SEM. n = 6-8. Letters denote significant differences between groups, a > b > c > d (P < 0.05) treatment increased serum leptin, it was significantly reduced after 24 h of tunicamycin challenge. Tunicamycin also reduced the leptin protein content in SAT, although the leptin gene expression was not reduced with respect to unstressed mice ( Figures 3A 3F, and 3G). In contrast, the increase in leptin protein and mRNA content in VAT in response to pioglitazone were not reduced after tunicamycin administration ( Figures 3A, 3F, and 3G). These results indicate that acute ER stress can impair the synthesis of secretory proteins such as adiponectin and leptin in SAT at a higher extent than in VAT, which associates with the circulating content of these ...
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... western blotting of mouse serum revealed that total and HMW adiponectin significantly increased after 8 h of tunicamycin administration but decreased after a 24 h tunicamycin challenge (Figures 3A and 3B). Pioglitazone significantly increased circulating adiponectin content with respect to control mice, but it was reduced after 24 h of tunicamycin administration. To evaluate the relative participa- tion of each adipose tissue depot in adiponectin synthesis, we measured adiponectin protein and mRNA abundance in SAT and VAT. Tunicamycin administration reduced adiponectin content in SAT, despite increased mRNA abundance. In contrast, adiponectin content in VAT was lower at 8 h of tunicamycin administration along with a reduction in mRNA content, but both protein abundance and mRNA content increased at 24 h to levels similar to that of the unstressed state ( Figures 3A, 3C, and 3D). Pioglitazone increased adiponectin content in both adipose tissue depots without a significant increase in its mRNA content. Induction of acute ER stress with tunicamycin decreased adiponectin protein content in both adipose tissue depots, however the reduction was more pronounced in SAT with respect to VAT ( Figures 3A, 3C, and 3D). To evaluate if leptin synthesis and secretion is also dependent on ER stress, we determined circulating leptin and leptin protein and mRNA abundance in adipose tissues. The circulating leptin concentration was not modified by acute ER stress as observed in mice administered with tunicamycin ( Figure 3E). However despite that 20 days of pioglitazone , and CHOP (D) and protein content of p-eIF2α, total eIF2α, p-JNK, and total JNK in adipose tissues (E), densitometric analysis of p-eIF2α/eIF2α (F) and p-JNK/JNK (G). Error bars represent SEM. n = 6-8. Letters denote significant differences between groups, a > b > c > d (P < 0.05) treatment increased serum leptin, it was significantly reduced after 24 h of tunicamycin challenge. Tunicamycin also reduced the leptin protein content in SAT, although the leptin gene expression was not reduced with respect to unstressed mice ( Figures 3A 3F, and 3G). In contrast, the increase in leptin protein and mRNA content in VAT in response to pioglitazone were not reduced after tunicamycin administration ( Figures 3A, 3F, and 3G). These results indicate that acute ER stress can impair the synthesis of secretory proteins such as adiponectin and leptin in SAT at a higher extent than in VAT, which associates with the circulating content of these ...
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... western blotting of mouse serum revealed that total and HMW adiponectin significantly increased after 8 h of tunicamycin administration but decreased after a 24 h tunicamycin challenge (Figures 3A and 3B). Pioglitazone significantly increased circulating adiponectin content with respect to control mice, but it was reduced after 24 h of tunicamycin administration. To evaluate the relative participa- tion of each adipose tissue depot in adiponectin synthesis, we measured adiponectin protein and mRNA abundance in SAT and VAT. Tunicamycin administration reduced adiponectin content in SAT, despite increased mRNA abundance. In contrast, adiponectin content in VAT was lower at 8 h of tunicamycin administration along with a reduction in mRNA content, but both protein abundance and mRNA content increased at 24 h to levels similar to that of the unstressed state ( Figures 3A, 3C, and 3D). Pioglitazone increased adiponectin content in both adipose tissue depots without a significant increase in its mRNA content. Induction of acute ER stress with tunicamycin decreased adiponectin protein content in both adipose tissue depots, however the reduction was more pronounced in SAT with respect to VAT ( Figures 3A, 3C, and 3D). To evaluate if leptin synthesis and secretion is also dependent on ER stress, we determined circulating leptin and leptin protein and mRNA abundance in adipose tissues. The circulating leptin concentration was not modified by acute ER stress as observed in mice administered with tunicamycin ( Figure 3E). However despite that 20 days of pioglitazone , and CHOP (D) and protein content of p-eIF2α, total eIF2α, p-JNK, and total JNK in adipose tissues (E), densitometric analysis of p-eIF2α/eIF2α (F) and p-JNK/JNK (G). Error bars represent SEM. n = 6-8. Letters denote significant differences between groups, a > b > c > d (P < 0.05) treatment increased serum leptin, it was significantly reduced after 24 h of tunicamycin challenge. Tunicamycin also reduced the leptin protein content in SAT, although the leptin gene expression was not reduced with respect to unstressed mice ( Figures 3A 3F, and 3G). In contrast, the increase in leptin protein and mRNA content in VAT in response to pioglitazone were not reduced after tunicamycin administration ( Figures 3A, 3F, and 3G). These results indicate that acute ER stress can impair the synthesis of secretory proteins such as adiponectin and leptin in SAT at a higher extent than in VAT, which associates with the circulating content of these ...
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... western blotting of mouse serum revealed that total and HMW adiponectin significantly increased after 8 h of tunicamycin administration but decreased after a 24 h tunicamycin challenge (Figures 3A and 3B). Pioglitazone significantly increased circulating adiponectin content with respect to control mice, but it was reduced after 24 h of tunicamycin administration. To evaluate the relative participa- tion of each adipose tissue depot in adiponectin synthesis, we measured adiponectin protein and mRNA abundance in SAT and VAT. Tunicamycin administration reduced adiponectin content in SAT, despite increased mRNA abundance. In contrast, adiponectin content in VAT was lower at 8 h of tunicamycin administration along with a reduction in mRNA content, but both protein abundance and mRNA content increased at 24 h to levels similar to that of the unstressed state ( Figures 3A, 3C, and 3D). Pioglitazone increased adiponectin content in both adipose tissue depots without a significant increase in its mRNA content. Induction of acute ER stress with tunicamycin decreased adiponectin protein content in both adipose tissue depots, however the reduction was more pronounced in SAT with respect to VAT ( Figures 3A, 3C, and 3D). To evaluate if leptin synthesis and secretion is also dependent on ER stress, we determined circulating leptin and leptin protein and mRNA abundance in adipose tissues. The circulating leptin concentration was not modified by acute ER stress as observed in mice administered with tunicamycin ( Figure 3E). However despite that 20 days of pioglitazone , and CHOP (D) and protein content of p-eIF2α, total eIF2α, p-JNK, and total JNK in adipose tissues (E), densitometric analysis of p-eIF2α/eIF2α (F) and p-JNK/JNK (G). Error bars represent SEM. n = 6-8. Letters denote significant differences between groups, a > b > c > d (P < 0.05) treatment increased serum leptin, it was significantly reduced after 24 h of tunicamycin challenge. Tunicamycin also reduced the leptin protein content in SAT, although the leptin gene expression was not reduced with respect to unstressed mice ( Figures 3A 3F, and 3G). In contrast, the increase in leptin protein and mRNA content in VAT in response to pioglitazone were not reduced after tunicamycin administration ( Figures 3A, 3F, and 3G). These results indicate that acute ER stress can impair the synthesis of secretory proteins such as adiponectin and leptin in SAT at a higher extent than in VAT, which associates with the circulating content of these ...
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Citations
... The activation of IRE1 leads to upregulation of c-Jun N-terminal kinase (JNK) and NF-κB, which induce the transcription of inflammatory genes, increase oxidative stress, and caspase-dependent apoptosis. ER stress impairs adipocyte metabolic function, leading to IR and reduced synthesis and secretion of adiponectin [114,117]. Adiponectin is exclusively produced by adipocytes, and it enhances insulin sensitivity and has anti-inflammatory properties. In dairy cows, lower secretion of adiponectin is directly correlated with diminished insulin sensitivity [118]. ...
During the periparturient period, dairy cows exhibit negative energy balance due to limited appetite and increased energy requirements for lactogenesis. The delicate equilibrium between energy availability and expenditure puts cows in a state of metabolic stress characterized by excessive lipolysis in white adipose tissues (AT), increased production of reactive oxygen species, and immune cell dysfunction. Metabolic stress, especially in AT, increases the risk for metabolic and inflammatory diseases. Around parturition, cows are also susceptible to endotoxemia. Bacterial-derived toxins cause endotoxemia by promoting inflammatory processes and immune cell infiltration in different organs and systems while impacting metabolic function by altering lipolysis, mitochondrial activity, and insulin sensitivity. In dairy cows, endotoxins enter the bloodstream after overcoming the defense mechanisms of the epithelial barriers, particularly during common periparturient conditions such as mastitis, metritis, and pneumonia, or after abrupt changes in the gut microbiome. In the bovine AT, endotoxins induce a pro-inflammatory response and stimulate lipolysis in AT, leading to the release of free fatty acids into the bloodstream. When excessive and protracted, endotoxin-induced lipolysis can impair adipocyte’s insulin signaling pathways and lipid synthesis. Endotoxin exposure can also induce oxidative stress in AT through the production of reactive oxygen species by inflammatory cells and other cellular components. This review provides insights into endotoxins’ impact on AT function, highlighting the gaps in our knowledge of the mechanisms underlying AT dysfunction, its connection with periparturient cows’ disease risk, and the need to develop effective interventions to prevent and treat endotoxemia-related inflammatory conditions in dairy cattle.
... However, we found an inverse correlation between insulin secretion and SC-WAT adipocytes area (p = 0.036). In obesity, the SC-WAT deposit, rather than visceral deposit, has been inversely associated also with adiponectin levels [59], probably because SC-WAT is more susceptible to endoplasmic reticu-lum stress, which reduces the synthesis and secretion of this adipokine [60]. Although, we did not find a positive correlation between glucose-stimulated insulin secretion and serum adiponectin concentration (p = 0.07; Fig. 7C), this correlation was obtained by Nakamura et al. [38] in a study with humans that illustrates the complex crosstalk between pancreatic β-cell and adipose tissue in obesity. ...
Background:
Obesity is a worldwide concern due to its global rapid expansion and remarkable impact on individual's health by predisposing to several other diseases. About twice as many women as men suffer from severe obesity and, in fact, there are stages in a woman's life when weight gain and adiposity can result in greater damage to health. For example, obesity triples the chance of a woman developing gestational diabetes. Many hormones promote the metabolic adaptations of pregnancy, including progesterone, whose role in female obesity is still not well known despite being involved in many physiological and pathological processes.
Methods:
Here we investigated whether progesterone treatment at low dose can worsen the glucose metabolism and the morpho functional aspects of adipose tissue and pancreas in obese females. Mice were assigned into four groups: normocaloric diet control (NO-CO), high-fat and -fructose diet control (HFF-CO), normocaloric diet plus progesterone (NO-PG) and high-fat and -fructose diet plus progesterone (HFF-PG) for 10 weeks. Infusion of progesterone (0.25 mg/kg/day) was done by osmotic minipump in the last 21 days of protocol.
Results:
Animals fed a hypercaloric diet exhibited obesity with increased body weight (p < 0.0001), adipocyte hypertrophy (p < 0.0001), hyperglycemia (p = 0.03), and glucose intolerance (p = 0.001). HFF-CO and HFF-PG groups showed lower adiponectin concentration (p < 0.0001) and glucose-stimulated insulin secretion (p = 0.03), without differences in islet size. Progesterone attenuated glucose intolerance in the HFF-PG group (p = 0.03), however, did not change morphology or endocrine function of adipose tissue and pancreatic islets.
Conclusions:
Taken together, our results showed that low dose of progesterone does not worsen the effects of hypercaloric diet in glycemic metabolism, morphology and function of adipose tissue and pancreatic islets in female animals. These results may improve the understanding of the mechanisms underlying the pathogenesis of obesity in women and eventually open new avenues for therapeutic strategies and better comprehension of the interactions between progesterone effects and obesity.
... 50 This suggests that ERS-induced adipose tissue inflammation may be related to the decrease of ADPN level. Torre et al 38 found that the reduction of ADPN synthesis was positively correlated with the increase of UPR markers in the visceral adipose tissue of obesity-induced ERS mice, and found that visceral fat lipolysis and circulating FFA were significantly increased in obese ERS mice compared with normal mice; After exposing subcutaneous primary adipocytes to drugs such as tunicamycin to induce ERS in vitro, maladaptive UPR also appeared in adipocytes, accompanied by decreased synthesis of ADPN and increased lipolysis. This suggests that ERS under obesity may affect lipolysis by inhibiting the secretion of ADPN and increase the release of FFA. ...
Adipose tissue dysfunction plays an important role in metabolic diseases associated with chronic inflammation, insulin resistance and lipid ectopic deposition in obese patients. In recent years, it has been found that under the stimulation of adipocyte endoplasmic reticulum stress (ERS), the over-activated ER unfolded protein response (UPR) exacerbates the inflammatory response of adipose tissue by interfering with the normal metabolism of adipose tissue, promotes the secretion of adipokines, and affects the browning and thermogenic pathways of adipose tissue, ultimately leading to the manifestation of metabolic syndrome such as ectopic lipid deposition and disorders of glucolipid metabolism in obese patients. This paper mainly summarizes the relationship between adipocyte ERS and obese adipose tissue dysfunction and provides an overview of the mechanisms by which ERS induces metabolic disorders such as catabolism, thermogenesis and inflammation in obese adipose tissue through the regulation of molecules and pathways such as NF-κB, ADPN, STAMP2, LPIN1, TRIP-Br2, NF-Y and SIRT2 and briefly describes the current mechanisms targeting adipocyte endoplasmic reticulum stress to improve obesity and provide ideas for intervention and treatment of obese adipose tissue dysfunction.
... Obesity, particularly abdominal obesity, along with its accomplice insulin resistance, also aggravates hyperandrogenism [37]. Obesity mainly manifests as increased levels of free fatty acids (FFAs), cholesterol, triglycerides and various apolipoprotein abnormalities [38]. Increased ...
Hyperandrogenism has been implicated in patients with polycystic ovary syndrome, which is the most common endocrine-metabolic disorder among women of reproductive age. Hyperandrogenism has been linked with renal disorders, particularly chronic kidney disease. Therefore, the present study investigated the effect of letrozole-induced hyperandrogenism on renal function in female Wistar rats. Eight-week-old female Wistar rats were allotted into two groups (n=6 per group) which include: Control, and letrozole-treated (LET). The control group received vehicle (p.o.) and the LET-treated group received letrozole (1 mg/kg; p.o.). The administration was carried out once daily for 21 days. The results showed that the hyperandrogenic rats had increased kidney weight, metabolic profile (fasting insulin and homeostatic model of assessment of insulin resistance), renal free fatty acids, renal inflammatory biomarkers (tumor necrosis factor and interleukin-6), renal malondialdehyde, γ-glutamyl transferase, lactate production, lactate dehydrogenase, plasma creatinine and urea, and plasma and renal uric acid with a subsequent decrease in renal glutathione peroxidase. Moreover, the study revealed an increased plasma testosterone level when compared with control animals. The present study therefore indicates that letrozole-induced hyperandrogenism resulted in elevated levels of testosterone and insulin resistance which causes renal dysfunction, further accompanied by renal lipid peroxidation and inflammation.
... The most likely etiology of PCOS is functional ovarian hyperandrogenism. Hyperandrogenism causes a series of pathophysiological changes in PCOS patients, including insulin resistance (21), hyperinsulinemia, and dyslipidemia (22), and conversely, hyperinsulinemia and obesity in PCOS play an important role in the establishment of hyperandrogenism (23). Hyperinsulinemia stimulates the production of ovarian androgens through its effects on the fully functional post-receptor MAP-K insulin pathway (24), and insulin also suppresses the hepatic production of SHBG, thereby accounting for the suppressed serum levels of SHBG in PCOS (25,26). ...
Purpose
This study aimed to investigate the increase in bone marrow adipose tissue (BMAT) in overweight and obese women with polycystic ovary syndrome (PCOS) and its relationship with hyperandrogenism, obesity, and metabolic disorders.
Methods
The study included 87 overweight or obese women with PCOS (mean age 29 ± 4 years), as well as 87 age-matched controls recruited from a separate population study. All PCOS patients were measured for anthropometric features, abdominal adipose tissue areas, BMAT, biochemistry, and sex hormones. BMAT was compared between the PCOS patients and controls. In PCOS patients, subgroup comparisons of BMAT and its associations with body adiposity indices, biochemistry, and sex hormones were analyzed. The odds ratios (ORs) of elevated BMAT (defined as BMAT ≥ 38%) were calculated.
Results
On average BMAT was increased by 5.6% ( ± 11.3%) in PCOS patients compared to controls. BMAT were significantly higher in the upper tertiles of total cholesterol (TC) and low density lipoprotein-cholesterol (LDL-C). BMAT was not correlated with abdominal adiposity indices or biochemistry except for LDL-C (r = 0.253—0.263, p = 0.014—0.018). LDL-C was not significantly different between the normal and abnormal androgen PCOS subgroups ( p = 0.10-0.887). LDL-C, follicle stimulating hormone (FSH), and total testosterone (TT) were risk factors for elevated BMAT, with ORs of 1.899 ( p = 0.038-0.040), 1.369 ( p = 0.030-0.042), and 1.002 ( p = 0.040-0.044) for each unit increase, respectively.
Conclusion
BMAT was increased in overweight and obese PCOS patients, but the increase in BMAT was not associated with the hyperandrogenism related obesity or metabolic disorders.
... Black lines indicate beneficial effects of UPR. Chronical or terminal UPR leads to β cell insulin desensitization in other organs, for one reason that ER stress is linked to reduced adiponectin secretion, [254][255][256] and for another reason that the PERK arm can elevate circulating levels of tumor necrosis factor α (TNFα), interleukin-6 (IL-6), and IL-1β. 251,257 All of these impose a vicious ER stress feedback and further exacerbate the adipose tissue per se and systemic IR. 258 In the skeletal muscle, aberrant activation of UPR pathways is also found in patients with T2DM and pregnant women with obesity or gestational diabetes. ...
Type 2 diabetes mellitus (T2DM) represents one of the fastest growing epidemic metabolic disorders worldwide and is a strong contributor for a broad range of comorbidities, including vascular, visual, neurological, kidney, and liver diseases. Moreover, recent data suggest a mutual interplay between T2DM and Corona Virus Disease 2019 (COVID-19). T2DM is characterized by insulin resistance (IR) and pancreatic β cell dysfunction. Pioneering discoveries throughout the past few decades have established notable links between signaling pathways and T2DM pathogenesis and therapy. Importantly, a number of signaling pathways substantially control the advancement of core pathological changes in T2DM, including IR and β cell dysfunction, as well as additional pathogenic disturbances. Accordingly, an improved understanding of these signaling pathways sheds light on tractable targets and strategies for developing and repurposing critical therapies to treat T2DM and its complications. In this review, we provide a brief overview of the history of T2DM and signaling pathways, and offer a systematic update on the role and mechanism of key signaling pathways underlying the onset, development, and progression of T2DM. In this content, we also summarize current therapeutic drugs/agents associated with signaling pathways for the treatment of T2DM and its complications, and discuss some implications and directions to the future of this field.
... However, chronic overnutrition reduces PPAR gamma activity, preventing further adipose tissue expansion, which leads to adipocyte hypertrophy and dysfunction ( Figure 7A-O). Dysfunctional adipocytes are characterized by reduced adiponectin synthesis and secretion, unrestrained lipolysis and adipocyte death [39]. Adipocyte death induces macrophage infiltration which in turn synthesizes and release pro-inflammatory cytokines such as TNF alpha ( Figure 7I) Increased local TNF alpha along with systemic LPS exacerbates adipose tissue dysfunction through reduction in PPAR gamma transcriptional activity [40]. ...
Pecans (Carya illinoinensis) are considered a functional food due to the high content of polyunsaturated fatty acids, dietary fiber and polyphenols. To determine the effect of whole pecans (WP) or a pecan polyphenol (PP) extract on the development of metabolic abnormalities in mice fed a high-fat (HF) diet, we fed C57BL/6 mice with a Control diet (7% fat), HF diet (23% fat), HF containing 30% WP or an HF diet supplemented with 3.6 or 6 mg/g of PP for 18 weeks. Supplementation of an HF diet with WP or PP reduced fat mass, serum cholesterol, insulin and HOMA-IR by 44, 40, 74 and 91%, respectively, compared to the HF diet. They also enhanced glucose tolerance by 37%, prevented pancreatic islet hypertrophy, and increased oxygen consumption by 27% compared to the HF diet. These beneficial effects were associated with increased thermogenic activity in brown adipose tissue, mitochondrial activity and AMPK activation in skeletal muscle, reduced hypertrophy and macrophage infiltration of subcutaneous and visceral adipocytes, reduced hepatic lipid content and enhanced metabolic signaling. Moreover, the microbial diversity of mice fed WP or PP was higher than those fed HF, and associated with lower circulating lipopolysaccharides (~83–95%). Additionally, a 4-week intervention study with the HF 6PP diet reduced the metabolic abnormalities of obese mice. The present study demonstrates that WP or a PP extract prevented obesity, liver steatosis and diabetes by reducing dysbiosis, inflammation, and increasing mitochondrial content and energy expenditure. Pecan polyphenols were mainly condensed tannin and ellagic acid derivatives including ellagitannins as determined by LC-MS. Herein we also propose a model for the progression of the HF diet-mediated metabolic disorder based on early and late events, and the possible molecular targets of WP and PP extract in preventive and intervention strategies. The body surface area normalization equation gave a conversion equivalent to a daily human intake dose of 2101–3502 mg phenolics that can be obtained from 110–183 g pecan kernels/day (22–38 whole pecans) or 21.6–36 g defatted pecan flour/day for an average person of 60 kg. This work lays the groundwork for future clinical studies.
... In addition, C/EBPα also is a part of adipogenesis-related genes, which can be induced by C/EBPβ that is expressed at the early stage of differentiation (Kita et al. 2018). Adiponectin is a kind of adipokine produced in adipose tissues, and the mice overexpressed with Adiponectin showed morbid obesity and increased subcutaneous fat (Torre-Villalvazo et al. 2018), suggesting that Adiponectin is critical for adipogenesis. Moreover, it has been confirmed that FABP4 and FABP5 were less expressed in adipose-derived stem cells (ADSCs), but they were induced and secreted by ADSCs after differentiation (Yamamoto et al. 2013). ...
The functions of tumour protein, translationally controlled 1 (TPT1), have been extensively researched in various cell types. Although TPT1 was reported to have accelerating effects on the lipid deposition of mouse hepatocytes, and the activation roles in phosphatidylinositol 3 kinase (PI3K/AKT) pathway, its role in the differentiation of ovine stromal vascular fractions (SVFs) and their underlying mechanisms have not been addressed. Therefore, the objective of this study was to explore whether TPT1 participates in the adipogenic differentiation regulation of ovine SVFs and the underlying mechanisms. The results from this study revealed that TPT1 was abundant in the tail fat of sheep and the protein was located in the nucleus of C3H10T1/2 cell line and ovine SVFs. Moreover, TPT1 expression was up-regulated during the adipogenic differentiation of SVFs. The overexpression of TPT1 dramatically accelerated the adipogenic differentiation of SVFs, accompanied by the up-regulation of adipogenic marker genes, while TPT1 inhibition had opposite effects. TPT1 also had a negative effect on forkhead box O1 (FOXO1). The PI3K/AKT pathway was involved in the promotion of adipogenesis induced by overexpressing TPT1. We concluded that TPT1 promotes the adipogenic differentiation of ovine SVFs through PI3K/AKT-dependent pathway and attenuates the expression of FOXO1 in ovine SVFs.
... 2,3 Several mechanisms that impair adipocyte function during obesity have been described, and endoplasmic reticulum (ER) stress has been identified as a common cause of increased lipolysis and adiponectin hyposecretion. 4 The ER is the organelle responsible for the synthesis, folding, and trafficking of secretory and membrane-associated proteins. In adipocytes, the ER is directly involved in the formation of lipid droplets and maintenance of lipid homeostasis. ...
Obesity is an increasing global public health problem. A strategy to treat obesity is the use of functional foods. Edible and medicinal mushrooms contain diverse bioactive compounds showing important antihyperlipidemic, antioxidant, and prebiotic properties. We analysed the effects of adding (10%) of Pleurotus ostreatus (Po, basidiomata), Ganoderma lucidum (Gl, basidiomata), or Ustilago maydis (Um, galls), milled, to a high fat plus saccharose diet (HFD + S) for 6 months in a model of obesity with Wistar rats. We assessed weight gain, body composition, lipid parameters, endoplasmic reticulum stress (proteins and inflammatory markers: BiP, XBP-1, JNK, p-JNK, TNF-α), and adiponectin in subcutaneous adipose tissue (SAT). The consumption of edible and medicinal mushrooms decreased weight gain (-17.2-30.1%) and fat mass (-23.7-43.1%), maintained fat-free mass, reduced levels of serum biochemical parameters (TC: -40.1-44.1%, TG: -37.7-51.6%, LDL-C: -64.5-71.1%), and prevented adipocyte hypertrophy (-30.9-36.9%) and collagen deposition (-70.9-73.7%) in SAT. Compared with the HFD + S group, mushroom consumption by Wistar rats significantly reduced the expression of proteins associated with endoplasmic reticulum stress and inflammation (BiP: -72.2-88.2%; XBP-1: -71.5-81.8%; JNK: -71.2-90.0%; p-JNK: -37.3-81.0%; TNF-α: -80.7-91.5%), whereas significantly increased adiponectin protein expression (246.4-654.2%) in SAT. These effects outperformed those obtained through the commercial lipid-lowering drug atorvastatin, contributing synergistically to prevent further obesity-related dysfunctions, such as insulin resistance derived from inflammation and ER stress in adipose tissue. Bioactive compounds from edible, functional and medicinal mushrooms represent new emerging therapies for obesity treatments using natural products.
... ER stress has been associated with dysfunctional WAT and BAT during obesity. In WAT, high-fat diet (HFD)-induced obesity enhances expression of UPR markers such as PERK, ATF-6, IRE1-a, ATF-4, and CHOP (29)(30)(31). Furthermore, ER stress affects adipokine secretion and action by impairing adiponectin synthesis and secretion (30,31) and by inducing leptin resistance (32). Lipogenesis and adipogenesis are also modulated by ER stress (33). ...
... In WAT, high-fat diet (HFD)-induced obesity enhances expression of UPR markers such as PERK, ATF-6, IRE1-a, ATF-4, and CHOP (29)(30)(31). Furthermore, ER stress affects adipokine secretion and action by impairing adiponectin synthesis and secretion (30,31) and by inducing leptin resistance (32). Lipogenesis and adipogenesis are also modulated by ER stress (33). ...
Adipose tissue is an organ with metabolic and endocrine activity. White, brown and ectopic adipose tissues have different structure, location, and function. Adipose tissue regulates energy homeostasis, providing energy in nutrient-deficient conditions and storing it in high-supply conditions. To attend to the high demand for energy storage during obesity, the adipose tissue undergoes morphological, functional and molecular changes. Endoplasmic reticulum (ER) stress has been evidenced as a molecular hallmark of metabolic disorders. In this sense, the ER stress inhibitor tauroursodeoxycholic acid (TUDCA), a bile acid conjugated to taurine with chemical chaperone activity, has emerged as a therapeutic strategy to minimize adipose tissue dysfunction and metabolic alterations associated with obesity. In this review, we highlight the effects of TUDCA and receptors TGR5 and FXR on adipose tissue in the setting of obesity. TUDCA has been demonstrated to limit metabolic disturbs associated to obesity by inhibiting ER stress, inflammation, and apoptosis in adipocytes. The beneficial effect of TUDCA on perivascular adipose tissue (PVAT) function and adiponectin release may be related to cardiovascular protection in obesity, although more studies are needed to clarify the mechanisms. Therefore, TUDCA has emerged as a potential therapeutic strategy for obesity and comorbidities.
