Perilipin 5 links mitochondrial uncoupled respiration in brown fat to healthy white fat remodeling and systemic glucose tolerance

Autor: Perry E. Bickel, Chaofeng Yang, Joshua A. Johnson, Violeta I. Gallardo-Montejano, John L. McAfee, William L. Holland, Lisa Hahner, Rodrigo Fernandez-Valdivia
Jazyk: angličtina
Rok vydání: 2021
Předmět:
0301 basic medicine
Male
General Physics and Astronomy
Adipose tissue
White adipose tissue
Mice
0302 clinical medicine
Adipose Tissue
Brown
Sirtuin 1
Non-alcoholic Fatty Liver Disease
Lipid droplet
Brown adipose tissue
Respiratory function
Lipid signalling
Uncoupling Protein 1
Multidisciplinary
Thermogenesis
Cell biology
Mitochondria
Up-Regulation
Cold Temperature
medicine.anatomical_structure
Adipose Tissue
White
Science
030209 endocrinology & metabolism
Adrenergic beta-3 Receptor Agonists
Mice
Transgenic
Dioxoles
Biology
Carbohydrate metabolism
Diet
High-Fat
Models
Biological
Perilipin-5
General Biochemistry
Genetics and Molecular Biology
Article
03 medical and health sciences
Insulin resistance
medicine
Animals
Humans
General Chemistry
Lipase
Energy metabolism
medicine.disease
Mice
Inbred C57BL
030104 developmental biology
Glucose
Perilipin
Insulin Resistance
Zdroj: Nature Communications, Vol 12, Iss 1, Pp 1-18 (2021)
Nature Communications
ISSN: 2041-1723
Popis: Exposure of mice or humans to cold promotes significant changes in brown adipose tissue (BAT) with respect to histology, lipid content, gene expression, and mitochondrial mass and function. Herein we report that the lipid droplet coat protein Perilipin 5 (PLIN5) increases markedly in BAT during exposure of mice to cold. To understand the functional significance of cold-induced PLIN5, we created and characterized gain- and loss-of-function mouse models. Enforcing PLIN5 expression in mouse BAT mimics the effects of cold with respect to mitochondrial cristae packing and uncoupled substrate-driven respiration. PLIN5 is necessary for the maintenance of mitochondrial cristae structure and respiratory function during cold stress. We further show that promoting PLIN5 function in BAT is associated with healthy remodeling of subcutaneous white adipose tissue and improvements in systemic glucose tolerance and diet-induced hepatic steatosis. These observations will inform future strategies that seek to exploit thermogenic adipose tissue as a therapeutic target for type 2 diabetes, obesity, and nonalcoholic fatty liver disease.
Perilipin 5 is a lipid droplet protein that interacts with PGC1α in the nucleus to regulate mitochondrial metabolism. Here the authors use genetically engineered mouse models to determine the physiologic role of Perilipin 5, and show that it regulates mitochondrial adaptations to cold, as well as systemic energy metabolism.
Databáze: OpenAIRE
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