Figure 1 - available from: Scientific Reports
This content is subject to copyright. Terms and conditions apply.
Microencapsulated murine subcutaneous WT and A1KO adipocytes reduced waist circumference. (A) The infrared images of dogs (EP, and AF are initials of individual dogs) illustrate the side of injection of encapsulated WT (white arrow) and aldehyde dehydrogenase a1 knock out (A1KO, brown arrow) adipocytes before (Pre) and 28 days after injection (Post). (B) Waist circumference (difference between waiste and nipples) was measured in dogs before and 28 days after treatment with encapsulated WT (white arrow) and A1KO as described in (Fig. S1). Paired Student t-test.
Source publication
Visceral obesity increases risks for all-cause mortality worldwide. A small population of thermogenic adipocytes expressing uncoupling protein-1 (Ucp1) regulates energy dissipation in white adipose tissue (WAT) depots. Thermogenic adipocytes subsets decrease obesity in mice, but their efficacy has not been tested in obese large animals. Here we enc...
Contexts in source publication
Context 1
... eliminate inter-individual variations in responses to these cells among dogs, we performed ultrasound guided injections to insert the encapsulated WT and A1KO cells (10 6 cells/type/side) on each side of the falciform WAT depot in every dog (n = 6). The infrared images of individual dogs (EP, and AF are initials of two randomly selected dogs) in Fig. 1A show the side of implantation of encapsulated WT (white arrow) and A1KO (brown arrow) adipocytes before and 28 days after implantation. We used these images to calculate relative changes in waist circumference pre and post procedure relative to the permanent position of mammary papillas in dogs (Fig. S1). The implantation of ...
Context 2
... initials of two randomly selected dogs) in Fig. 1A show the side of implantation of encapsulated WT (white arrow) and A1KO (brown arrow) adipocytes before and 28 days after implantation. We used these images to calculate relative changes in waist circumference pre and post procedure relative to the permanent position of mammary papillas in dogs (Fig. S1). The implantation of encapsulated mouse adipocytes significantly reduced relative waist circumference post procedure (12 ± 5% range 6-20%) compared to waist circumference before procedure (100%) (Fig. ...
Context 3
... to calculate relative changes in waist circumference pre and post procedure relative to the permanent position of mammary papillas in dogs (Fig. S1). The implantation of encapsulated mouse adipocytes significantly reduced relative waist circumference post procedure (12 ± 5% range 6-20%) compared to waist circumference before procedure (100%) (Fig. ...
Similar publications
Obesity and related comorbidities are a major health concern. The drugs used to treat these conditions are largely inadequate or dangerous, and a well-researched approach based on nutraceuticals would be highly useful. Pterostilbene (Pt), i.e., 3,5-dimethylresveratrol, has been reported to be effective in animal models of obesity, acting on differe...
Citations
... 24 Moreover, Aldh1a1 deficient adipocytes were shown not only to effectively reduce body weight of mice fed a highfat diet (HFD), 25,26 but also they markedly reduced waist circumference, body weight, and fat mass when implanted into visceral fat depots of obese large animal models such as dogs. 27 Additionally, Aldh1a1-deficient mice are viable and do not show any growth or survival defects. 28 Thus, inhibiting the function of Aldh1a1 is clearly an attractive approach to treating obesity. ...
Background and objectives:
A drug repurposing strategy is an approach for identifying new therapeutic uses for approved or investigational drugs. Thanks to the moderate cost of repurposing a drug compared to bringing new chemical entity to the market, drug repurposing is rapidly gaining ground. The aim of this work is to study the anti-obesity effect of disulfiram (DSF), an irreversible aldehyde dehydrogenase inhibitor approved by the Food and Drug Administration (FDA) to treat chronic alcoholism since 1951.
Methods:
Thirty male Albino rats were randomly assigned to six groups. G1, the control group, was given a standard diet. G2, the positive control group, was given a high-fat diet (HFD). G3 was given an HFD, and DSF 50 mg/kg/day was administered orally from day one for six weeks. G4 was given an HFD, and DSF 200 mg/kg/day was administered orally from day one for six weeks. G5 was given an HFD for six weeks; then treatment started with 50 mg/kg/day DSF orally. G6 was given an HFD for six weeks; then treatment started with 200 mg/kg/day DSF orally for three weeks. The body weight, food consumption and blood glucose levels were monitored over the given time interval.
Results:
Both doses of DSF significantly limited the body weight gain caused by an HFD for the treated animals. HF-fed rats received 50 and 200 mg/kg/day of DSF had their body weight increased by 51.93 ± 7.89% and 20.88 ± 15.05% respectively, whereas the body weight of control animals increased by 93.1 ± 20.04%. DSF also significantly decreased the body weight of obese animals. At 50 and 200 mg/kg/day of DSF, HF-fed rats lost 16.74 ± 8.61% and 23.9 ± 3.93% respectively, as their untreated counterparts had their body weight increased by 11.85 ± 3.79% after three weeks of treatment, thus restoring a body weight matching those who received a standard diet.
Conclusion:
FDA-approved disulfiram has a strong anti-obesity effect on HFD-fed rats.
Disulfiram is an FDA-approved drug used to treat chronic alcoholism. This drug works by blocking the second step of ethanol metabolism by inhibiting aldehyde dehydrogenase-2 (ALDH2), the enzyme responsible for acetaldehyde oxidation into acetic acid. This leads to the accumulation of acetaldehyde in the blood following alcohol ingestion and to highly unpleasant symptoms known as acetaldehyde syndrome. Disulfiram also inhibits ALDH1a1, another member of the aldehyde dehydrogenases that catalyzes the oxidation of retinal into retinoic acid. ALDH1a1 represents a key therapeutic target for the treatment of important diseases such as cancer and obesity. The substrate tunnel is larger in ALDH1a1 than in ALDH2; therefore. Thus, replacing disulfiram ethyl groups with larger groups will yield selective ALDH1a1 inhibitors. In this work, we successfully synthesized derivative 2b, in which two ethyl groups were replaced by two para fluorobenzyl groups. The 2b derivative showed a comparable activity to disulfiram against ALDH1a1; however, it was completely devoid of inhibitory activity against ALDH2.
