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

Author

Listed:
  • 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
    VA San Diego Healthcare System)

  • Michael Petrascheck

    (The Scripps Research Institute)

  • Olivia Osborn

    (University of California San Diego)

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.

Suggested Citation

  • Rizaldy C. Zapata & Maria Carretero & Felipe Castellani Gomes Reis & Besma S. Chaudry & Jachelle Ofrecio & Dinghong Zhang & Roman Sasik & Theodore Ciaraldi & Michael Petrascheck & Olivia Osborn, 2022. "Adipocytes control food intake and weight regain via Vacuolar-type H+ ATPase," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-32764-5
    DOI: 10.1038/s41467-022-32764-5
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    References listed on IDEAS

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    2. Anabel Perez-Gomez & Maria Carretero & Natalie Weber & Veronika Peterka & Alan To & Viktoriya Titova & Gregory Solis & Olivia Osborn & Michael Petrascheck, 2018. "A phenotypic Caenorhabditis elegans screen identifies a selective suppressor of antipsychotic-induced hyperphagia," Nature Communications, Nature, vol. 9(1), pages 1-12, December.
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