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Perilipin (PLIN) is a class of protein-coating lipid droplets in adipocytes. We aimed to examine the association between common single-nucleotide polymorphisms (SNPs) at PLIN locus with circulating free fatty acid (FFA) and abdominal fat distribution in response to weight loss.
Non-diabetic/overweight-obese Koreans (n=177) participated in a 12-week...
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... DNA was extracted from 5 ml of whole blood using a commercially available DNA isolation kit (WIZARD R Genomic DNA purification kit, Promega Corp., Madison, WI, USA) according to the manufacturer's protocol. We genotyped seven previously reported SNPs (6209T4C, 10076C4G, 10171A4T, 11482G4A, 13042A4G, 13048C4T and 14995A4T) 8,10,11 (Figure 1). Each genotyping was performed by SNP-ITt assays using single-primer extension technology (SNPstream 25Kt System, Orchid Biosystems, NJ, USA). ...
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CGI-58/ABHD5 co-activates adipose triglyceride lipase (ATGL). In adipocytes, CGI-58 binds to perilipin 1A on lipid droplets under basal conditions, preventing interaction with ATGL. Upon activation of protein kinase A (PKA), perilipin 1A is phosphorylated and CGI-58 rapidly disperses into the cytoplasm, enabling lipase co-activation. Since the amin...
Increased adipocyte lipolysis links obesity to insulin resistance. The lipid droplet coating-protein Perilipin participates in regulation of lipolysis and is implicated in obesity. In the present study we investigate epigenetic regulation of the PLIN1 gene by correlating PLIN1 CpG methylation to gene expression and lipolysis, and functionally evalu...
Perilipins (PLINs) play a key role in energy storage by orchestrating the activity of lipases on the surface of lipid droplets
(LDs). Failure of this activity results in severe metabolic disease in humans. Unlike all other lipid droplet associated proteins,
PLINs localise almost exclusively to the phospholipid monolayer surrounding the droplet. To...
The surface of lipid droplets (LDs) in various cell types is coated with perilipin proteins encoded by the Plin genes. Perilipins regulate LD metabolism by selectively recruiting lipases and other proteins to LDs. We have studied the expression of perilipins in mouse muscle. The glycolytic fiber-enriched gastrocnemius muscle expresses predominantly...
Citations
... They play a primary role in the regulation of lipid, glucose, and energy homeostasis through the formation and mobilization of adipocyte stores [206][207][208]. The PLIN1 (rs1052700) is an obesity risk factor [209][210][211], which is also associated with better weight loss outcomes [50,212]. Indeed, the minor alleles in rs2304795 and rs1052700 are associated with body fat, waist circumference, and obesity risk in Caucasian adult women [209]. ...
... In addition, the T allele in rs2304795 predisposes to the development of obesity in adolescence [211]. Examining the effect of rs1052700 polymorphism in response to diet modification, Jang et al. showed that carriers of the minor allele in rs894160 or rs1052700 of Korean origin showed a more significant decrease in waist circumference, fat mass, and free fatty acids, indicating increased lipolysis [206], during an energy-restricted weight loss intervention [212], similar to findings in Deram et al. [50]. Moreover, the rs894160 and rs1052700 were associated with a gene-diet interaction between increased saturated fatty acids and carbohydrate dietary intake and insulin resistance in Asian adult women [214]. ...
Overweight and obesity in childhood and adolescence represents one of the most challenging public health problems of our century owing to its epidemic proportions and the associated significant morbidity, mortality, and increase in public health costs. The pathogenesis of polygenic obesity is multifactorial and is due to the interaction among genetic, epigenetic, and environmental factors. More than 1100 independent genetic loci associated with obesity traits have been currently identified, and there is great interest in the decoding of their biological functions and the gene–environment interaction. The present study aimed to systematically review the scientific evidence and to explore the relation of single-nucleotide polymorphisms (SNPs) and copy number variants (CNVs) with changes in body mass index (BMI) and other measures of body composition in children and adolescents with obesity, as well as their response to lifestyle interventions. Twenty-seven studies were included in the qualitative synthesis, which consisted of 7928 overweight/obese children and adolescents at different stages of pubertal development who underwent multidisciplinary management. The effect of polymorphisms in 92 different genes was assessed and revealed SNPs in 24 genetic loci significantly associated with BMI and/or body composition change, which contribute to the complex metabolic imbalance of obesity, including the regulation of appetite and energy balance, the homeostasis of glucose, lipid, and adipose tissue, as well as their interactions. The decoding of the genetic and molecular/cellular pathophysiology of obesity and the gene–environment interactions, alongside with the individual genotype, will enable us to design targeted and personalized preventive and management interventions for obesity early in life.
... We hypothesized that the differences found in the effect of the polymorphism between boys and girls would be associated with the fact that the boys and girls in our population had significantly different leptin levels, and that plasma leptin levels could modulate the association of the polymorphisms with NEFA concentrations, which conditions its association with BMI and lipid metabolism. The PLIN1 rs894160 and PLIN1 rs1052700 have been associated with changes in abdominal fat and blood NEFA levels that occur in weight loss [41], which may also suggest an influence on these associations exerted by changes in leptin levels associated with changes in body weight. ...
Variations in the perilipin (PLIN) gene have been suggested to be associated with obesity
and its related alterations, but a different nutritional status seems to contribute to differences in these associations. In our study, we examined the association of several polymorphisms at the PLIN locus with obesity and lipid profile in children, and then analyzed the mediation of plasma leptin levels on these associations. The single-nucleotide polymorphisms (SNPs) rs894160, rs1052700, and rs2304795 in PLIN1, and rs35568725 in PLIN2, were analyzed by RT-PCR in 1264 children aged 6–8 years. Our
results showed a contrasting association of PLIN1 rs1052700 with apolipoprotein (Apo) A-I levels in boys and girls, with genotype TT carriers showing significantly higher Apo A-I levels in boys and significantly lower Apo A-I levels in girls. Significant associations of the SNP PLIN2 rs35568725 with high-density lipoprotein cholesterol (HDL-cholesterol), Apo A-I, and non-esterified fatty acids (NEFA) were observed in boys but not in girls. The associations of the SNPs studied with body mass index (BMI), NEFA, and Apo A-I in boys and girls were different depending on leptin concentration.In conclusion, we describe the mediation of plasma leptin levels in the association of SNPs in PLIN1 and PLIN2 with BMI, Apo A-I, and NEFA. Different leptin levels by sex may contribute to explain the
sex-dependent association of the PLIN SNPs with these variables.
... One study comparing perilipin levels in obese patients with metabolic syndrome found perilipin levels were higher in the obese subjects with metabolic syndrome than non-metabolic syndrome obese patients [12]. Variants in the PLIN gene have been identified and examined and were previously associated with obesity and high lipid levels in humans [13], [14], [15], [16], [17], [18] with controversial results. ...
... In the Korean population, Jang et al. studied women who were given a low-calorie diet (−300 kcal per day) and found that the presence of A11482 allele was associated with greater weight loss in response to calorie restriction and the weight loss occurred especially in the visceral fat compartment [18]. Carriers of A allele in 11482G > A polymorphisms have been found to be resistant to weight loss with calorie restriction and treatment with rosiglitazone as a peroxisome agonist receptor-γ [24]. ...
BACKGROUND: Perilipin is very important for the regulation of the deposition and mobilization of fats. The human perilipin gene (PLIN) is near the locus for risk of obesity and hypertriglyceridemia. The PLIN gene is thought to be involved in the occurrence of metabolic syndrome. AIM: The aim of this research is to determine the role of variations of the PLIN gene (PLN4 11482 G>A) as a risk factor for component of metabolic syndrome. METHODS: This study involved a total of 160 subjects consisting of 80 with metabolic syndrome and 80 controls. Genotype analysis was done with the polymerase chain reaction-restriction fragment length polymorphism method. The data were analyzed with t-tests to compare the subjects’ characteristics between metabolic syndrome groups and controls. Risk factors of PLIN genotypes were calculated with odds ratio and multivariate regression analysis was used to determine the role of the PLIN gene with each biochemical characteristic. RESULTS: The result was significant differences between the characteristics of the metabolic syndrome subjects with controls (p < 0.05). There was no difference in genotypes between patients with metabolic syndrome and controls. The multivariate analysis of the genetic role with biochemical components showed the PLIN gene in AA carriers as a risk factor for metabolic syndrome compare GA+GG, risk of obesity, and hypercholesterolemia with p < 0.05. CONCLUSION: It can be concluded that PLIN variation has a role in the incidence of metabolic syndrome, especially in relation to obesity and hypercholesterolemia. Further study is needed to determine the role of other gene variations as a risk factor for metabolic syndrome.
... This gene encodes the protein perilipin 1, a MBE major regulator of lipolysis and lipogenesis in adipocytes (Tansey et al. 2004). The ancestral G allele at this site has previously been associated with lower serum lipid levels (Jang et al. 2006;Song et al. 2015). In Siberia, the Nganasans and Yakuts have the highest allele frequencies of 0.55 and 0.45 respectively, with over 60% of individuals in both populations having at least one G allele (supplementary table S8, Supplementary Material online). ...
... For our specific candidate, rs6496589, CG and GG genotypes were found to be highly associated with risk of central obesity in Chinese adults, and in vitro assays indicated differences in lipid droplet accumulation between GG and CC genotypes, with GG homozygotes showing more, smaller droplets (Song et al. 2015). The GG genotype was also associated with lower circulating free fatty acid levels in Koreans following moderate weight loss (Jang et al. 2006). In our data, it is the G allele that Genomic Evidence of Local Adaptation . ...
The indigenous inhabitants of Siberia live in some of the harshest environments on earth, experiencing extended periods of severe cold temperatures, dramatic variation in photoperiod, and limited and highly variable food resources. While the successful long-term settlement of this area by humans required multiple behavioral and cultural innovations, the nature of the underlying genetic changes has generally remained elusive. In this study, we used a three-part approach to identify putative targets of positive natural selection in Siberians. We first performed selection scans on whole exome and genome-wide SNP array data from multiple Siberian populations. We then annotated candidates in the tails of the empirical distributions, focusing on candidates with evidence linking them to biological processes and phenotypes previously identified as relevant to adaptation in circumpolar groups. The top candidates were then genotyped in additional populations to determine their spatial allele frequency distributions and associations with climate variables. Our analysis reveals missense mutations in three genes involved in lipid metabolism (PLA2G2A, PLIN1, ANGPTL8) that exhibit genomic and spatial patterns consistent with selection for cold climate and/or diet. These variants are unified by their connection to brown adipose tissue, and may help to explain previously observed physiological differences in Siberians such as low serum lipid levels and increased basal metabolic rate. These results support the hypothesis that indigenous Siberians have genetically adapted to their local environment by selection on multiple genes.
... Soenen et al. [9] reported that men with the T/T genotype compared to the A/A-T/A genotype had a significantly lower weight, fat mass and fat-free mass at baseline and throughout the intervention, whereas women with the T/T genotype had a significantly lower plasma leptin level. In other studies, the analysis of weight loss and obesity risk in T-allele carriers of PLIN1 rs1052700 showed a lower obesity risk in women [29] and a higher weight loss after a weight-loss intervention in children and adults [30,31] , although one study reported a higher obesity risk in women [32] . Our results are in accordance with the data from most of these studies. ...
Background:
Weight loss success is determined by genetic factors, which may differ according to treatment strategy.
Methods:
From a multidisciplinary obesity treatment program involving dietary advice, psychological counseling, and increased physical activity, 587 subjects (68% female; 46.1 ± 12.4 years; BMI 39.9 ± 6.3) were recruited. At baseline, a blood sample was drawn for DNA isolation. Genotypes were determined for 30 polymorphisms in 25 candidate genes. The association between genotypes and weight loss was assessed after 3 months (short-term) and after 12 months of treatment (long-term). Weight loss was categorized as ≥5% or <5% of initial weight.
Results:
The G/G genotype of PLIN1 (rs2289487) and PLIN1 (rs2304795), the T/T genotype of PLIN1 (rs1052700), and the C/C genotype of MMP2 predicted ≥5% weight loss in the first 3 months. The C/G-G/G genotype of PPARγ (rs1801282) and the T/C genotype of TIMP4 (rs3755724) predicted ≥5% weight loss after 12 months. Subjects with the combination of PPARγ (rs1801282) C/G-G/G and TIMP4 (rs3755724) T/C lost even more weight.
Conclusion:
Polymorphisms in genes related to regulation of fat storage and structural adaptation of the adipocytes are predictors for weight loss success with different genes being relevant for short-term and long-term weight loss success.
... Our results may also explain some lack of consensus with regard to the association between the PLIN1 14995A.T SNP and obesity-related variables (20,24,44), and future studies related to PLIN1 should include food timing data to make more robust conclusions. Although the overall mechanism linking this SNP to anthropometric variables has not been experimentally shown, the PLIN1 14995A.T SNP is located in the 3# region where alternative splicing occurs, which may result in different PLIN1 isoforms with diverse lipolytic efficiency (43,44). As per the time interaction, there is a temporal component in the regulation of adipose tissue functions (45). ...
Background:
We propose that eating lunch late impairs the mobilization of fat from adipose tissue, particularly in carriers of PERILIPIN1 (PLIN1) variants.
Objective:
The aim was to test the hypothesis that PLIN1, a circadian lipid-stabilizing protein in the adipocyte, interacts with the timing of food intake to affect weight loss.
Design:
A total of 1287 overweight and obese subjects [229 men and 1058 women; mean ± SD body mass index (in kg/m(2)): 31 ± 5] who attended outpatient obesity clinics were enrolled in the ONTIME (Obesity, Nutrigenetics, Timing, Mediterranean) study. Timing of food intake was estimated with a validated questionnaire. Anthropometric variables and PLIN1 genotypes were analyzed, including 6209T>C (rs2289487), 11482G>A (rs894160), 13041A>G (rs2304795), and 14995A>T (rs1052700). The main outcomes were effectiveness of the program and weight-loss progression during 28 wk of treatment.
Results:
The PLIN1 locus was associated with variability in response to a weight-loss program. Specifically, carrying the minor C allele at the PLIN1 6209T>C was associated with better weight-loss response (P = 0.035). The probability of being a better responder [percentage of weight loss ≥7.5% (median)] was 33% higher among C than among TT carriers (OR: 1.32; 95% CI: 1.05, 1.67; P = 0.017). We found an interaction of PLIN1 × food timing between the 14995A>T variant and timing of lunch eating for total weight loss (P = 0.035). Among AA carriers, eating late was associated with less weight loss (P < 0.001), whereas time of eating did not influence weight loss among TT carriers (P = 0.326).
Conclusions:
Variability at the PLIN1 locus is associated with variability in weight loss. Moreover, eating late is related to lower weight-loss effectiveness among carriers of the AA genotype at the PLIN1 14995A>T variant. These results contribute to our ability to implement more precise and successful obesity treatments. The ONTIME study was registered at clinicaltrials.gov as NCT02829619.
... Other genetic variants located in or near some genes related to lipid metabolism, such as acyl-CoA synthetase long-chain family member 5 (ACSL5), perilipin 1 (PLIN1), fatty acid binding protein 2, intestinal (FABP2), and Niemann-Pick Disease, type C1 (NPC1), have been associated with resistance to body weight loss (49)(50)(51)(52)(53)(54)(55). ACSL5 ½AQ13 converts free long-chain FAs into fatty acyl-CoA, so it potentially plays an important role in lipid biosynthesis and FA degradation (56). ...
As obesity has become a major global public health challenge, a large number of studies have analyzed different strategies aimed at inducing a negative energy balance and, consequently, body weight loss. However, most existing weight loss programs are generally unsuccessful, so several interventions have been carried out to identify physiologic and behavioral factors concerning this variability in order to implement more personalized treatment. Nowadays, an individualized approach is being proposed through so-called personalized nutrition, whereby not only the phenotype but also the genotype is used for customized nutrition treatment. Regarding body weight regulation, ∼70 polymorphisms have been identified in or near genes related to energy expenditure, appetite, adipogenesis, insulin resistance, and lipid metabolism. Although personalized nutrition refers mainly to genetic makeup, recent advances in the investigation of the epigenome and the microbiome open the door to implement more personalized recommendations for body weight management. In this context, recent studies have demonstrated the existence of several epigenetic markers that may modify gene expression and could be involved in the outcome of weight loss interventions. Moreover, different studies have shown that dietary interventions could affect the composition of gut microbiota and have an impact on body weight. The integration of nutrigenetic, epigenetic, and metagenomic data may lead to the design of more personalized dietary treatments to prevent chronic diseases and to optimize the individual's response to dietary interventions.
... Previously, it was found that lipolysis in obese and overweight individual is impaired (1). Genetic studies showed that polymorphism of genes related lipolysis influenced weight loss in obese subjects during weight loss although results are still controversial (2)(3)(4)(5)(6)(7)(8). Furthermore, Rogge (9) proposed that fatty acid oxidation (FAO) is also an important factor that influences development of obesity in human. ...
Modulation of fat metabolism is an important component of the etiology of obesity as well as individual response to weight loss program. The influence of lipolysis process had receives many attentions in recent decades. Compared to that, fatty acid oxidation which occurred after lipolysis seems to be less exposed. There are limited publications on how fatty acid oxidation influences predisposition to obesity, especially the importance of genetic variations of fatty acid oxidation proteins on development of obesity. The aim of this review is to provide recent knowledge on how polymorphism of genes related fatty acid oxidation is obtained. Studies in human as well as animal model showed that disturbance of genes related fatty acid oxidation process gave impact on body weight and risks to obesity. Several polymorphisms on CD36, CPT, ACS and FABP had been shown to be related to obesity either by regulating enzymatic activity or directly influence fatty acid oxidation process.
... Intervention studies done from various countries such as The Netherlands, Spain, Korea and Brazil had raised promosing results that PLIN could be used as a predictor of weight loss but the results are still being questioned. (33)(34)(35)(36) Corella et al. (33) shown that obese subjects who had A allele of PLIN 11482G>A rs894160 reduced less weight while Jang et al. (34) showed no effect of this genotype. In Brazilian obese children and adolescents, Deram et al. (35) found that subjects with T allele of PLIN6 14995A>T rs1052700 reduced more weight after a lifestyle intervention. ...
... Intervention studies done from various countries such as The Netherlands, Spain, Korea and Brazil had raised promosing results that PLIN could be used as a predictor of weight loss but the results are still being questioned. (33)(34)(35)(36) Corella et al. (33) shown that obese subjects who had A allele of PLIN 11482G>A rs894160 reduced less weight while Jang et al. (34) showed no effect of this genotype. In Brazilian obese children and adolescents, Deram et al. (35) found that subjects with T allele of PLIN6 14995A>T rs1052700 reduced more weight after a lifestyle intervention. ...
... It is suspected that differences in weight loss treatment between each study were the reason each finding showed different outcomes. For example, study by Corella et al. (33) used 1,200 kcal a day as energy restriction program while Jang et al. (34) only used 300 kcal reductions a day. This difference could give a big impact in the amount of energy received. ...
The ability of obese people to reduce weight in the same treatment varied. Genetic make up as well as the behavioral changes are important for the successfulness of the program. One of the most proposed genetic variations that have been reported in many intervention studies was genes that control lipolysis process. This review summarizes studies that were done showing the influence of genetic polymorphisms in lipolysis pathway and weight loss in a weight loss treatment program. Some studies had shown that certain enzymes involved in this process were related to successfulness of weight loss program. Single Nucleotide Polymorphism (SNP) in PLIN (11482G>A) and ADRB3 (Trp64Arg) are the most studied polymorphisms that have effect on weight loss intervention. However, those studies were not conclusive because of limited number of subjects used and controversies in the results. Thus, replication and confirmation on the role of those genes in weight loss are important due to their potential to be used as predictors of the results of the program.
... Some SNPs located in genes related to lipid metabolism, such as perilipin (PLIN1), fatty acid binding protein-2 (FABP2), peroxisome proliferator-activated receptor (PPARG), or the apolipoproteins APOA5, APOE, APOA1, APOBR and APOA4, may also affect the outcome of weight loss programs (Tables 1e3). Thus, the rs894160 gene variant of PLIN1 has been associated with changes in abdominal fat reduction following a hypocaloric diet prescribed for mildly weight loss (Yang et al., 2006). Moreover, PLIN1 11482A carriers of the rs894160 polymorphism were apparently resistant to weight loss (Corella et al., 2005). ...
