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NOBEL PRIZE 2026

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NIHNATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASESR01

Ucp1-independent functions in brown and beige adipocytes

Completed
Institution
UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, CA
Principal investigator
Biao Wang
Funding
$519K
Duration
2021–2026
Open portfolio

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Abstract

ABSTRACT Uncoupling protein 1/Ucp1-mediated adaptive thermogenesis in brown adipose tissue/BAT is essential for thermoregulation and energy balance. Increasing adaptive thermogenesis in human brown fat has been considered as an alternative strategy to increase energy expenditure, and ultimately to improve metabolic health, since brown fat activity gradually declines with aging and metabolic diseases. Our previous work identified a unique phenomenon that brown adipocyte-specific Lrpprc knockout mice can trade off mitochondria-fueled Ucp1-dependent thermogenesis in BAT for systemic metabolic fitness. This proposal will use this new mouse model to investigate Ucp1-independent functions. Aim 1 will investigate the underlying mechanisms of the ATF4-driven thermogenesis in brown adipocytes. Aim 2 will determine the physiological regulation of this process. Aim 3 will address its metabolic contributions to systemic metabolism. Collectively, this proposal will reveal novel functions of brown (and/or beige) adipocytes beyond Ucp1-dependent thermogenesis.

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R01NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASESPathophysiology of Obesity and Metabolic Disease Study Section[POMD]beigethermogenesisadipocytesmetabolicbrownbatuncouplingfat

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