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RRC ID 76337
著者 Zapata RC, Carretero M, Reis FCG, Chaudry BS, Ofrecio J, Zhang D, Sasik R, Ciaraldi T, Petrascheck M, Osborn O.
タイトル Adipocytes control food intake and weight regain via Vacuolar-type H+ ATPase.
ジャーナル 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.
巻・号 13(1)
ページ 5092
公開日 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
リソース情報
線虫 tm5764 tm6310