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 |
Externí odkaz: |