| RRC ID |
76337
|
| Author |
Zapata RC, Carretero M, Reis FCG, Chaudry BS, Ofrecio J, Zhang D, Sasik R, Ciaraldi T, Petrascheck M, Osborn O.
|
| Title |
Adipocytes control food intake and weight regain via Vacuolar-type H+ ATPase.
|
| Journal |
Nat Commun
|
| Abstract |
Energy metabolism becomes dysregulated in individuals with obesity and many of these changes persist after weight loss and likely play a role in weight regain. In these studies, we use a mouse model of diet-induced obesity and weight loss to study the transcriptional memory of obesity. We found that the 'metabolic memory' of obesity is predominantly localized in adipocytes. Utilizing a C. elegans-based food intake assay, we identify 'metabolic memory' genes that play a role in food intake regulation. We show that expression of ATP6v0a1, a subunit of V-ATPase, is significantly induced in both obese mouse and human adipocytes that persists after weight loss. C. elegans mutants deficient in Atp6v0A1/unc32 eat less than WT controls. Adipocyte-specific Atp6v0a1 knockout mice have reduced food intake and gain less weight in response to HFD. Pharmacological disruption of V-ATPase assembly leads to decreased food intake and less weight re-gain. In summary, using a series of genetic tools from invertebrates to vertebrates, we identify ATP6v0a1 as a regulator of peripheral metabolic memory, providing a potential target for regulation of food intake, weight loss maintenance and the treatment of obesity.
|
| Volume |
13(1)
|
| Pages |
5092
|
| Published |
2022-8-30
|
| DOI |
10.1038/s41467-022-32764-5
|
| PII |
10.1038/s41467-022-32764-5
|
| PMID |
36042358
|
| PMC |
PMC9427743
|
| MeSH |
Adipocytes / metabolism
Animals
Caenorhabditis elegans / genetics
Caenorhabditis elegans / metabolism
Diet, High-Fat* / adverse effects
Eating / physiology
Humans
Mice
Mice, Inbred C57BL
Mice, Obese
Obesity* / genetics
Obesity* / metabolism
Vacuolar Proton-Translocating ATPases / genetics
Vacuolar Proton-Translocating ATPases / metabolism*
Weight Gain
Weight Loss
|
| Resource |
| C.elegans |
tm5764
tm6310 |
