Adipocytes control food intake and weight regain via Vacuolar-type H+ ATPase

Rizaldy C. Zapata, Maria Carretero, Felipe Castellani Gomes Reis, Besma S. Chaudry, Jachelle Ofrecio, Dinghong Zhang, Roman Sasik, Theodore Ciaraldi, Michael Petrascheck and Olivia Osborn ()
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Rizaldy C. Zapata: University of California San Diego
Maria Carretero: The Scripps Research Institute
Felipe Castellani Gomes Reis: University of California San Diego
Besma S. Chaudry: University of California San Diego
Jachelle Ofrecio: University of California San Diego
Dinghong Zhang: University of California San Diego
Roman Sasik: University of California San Diego
Theodore Ciaraldi: University of California San Diego
Michael Petrascheck: The Scripps Research Institute
Olivia Osborn: University of California San Diego

Nature Communications, 2022, vol. 13, issue 1, 1-15

Abstract: 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.

Date: 2022
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DOI: 10.1038/s41467-022-32764-5

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