Ectopic brown adipose tissue in muscle provides a mechanism for differences in risk of metabolic syndrome in mice

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 104; no. 7; pp. 2366 - 2371
• Main Authors: Almind, Katrine, Manieri, Monia, Sivitz, William I, Cinti, Saverio, Kahn, C. Ronald
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 13.02.2007; National Acad Sciences
• Subjects: adipocytes; Adipose tissue; Adipose Tissue, Brown - chemistry; Adipose Tissue, Brown - metabolism; Adipose Tissue, Brown - physiology; Adipose Tissue, Brown - ultrastructure; Agonists; Animals; Biological Sciences; Brown adipose tissue; cell respiration; Diabetes; Dietary Fats - administration & dosage; Dietary Fats - adverse effects; electron transport chain; Energy Metabolism; Gene expression; High fat diet; intermuscular adipose tissue; intermuscular fat; Ion Channels - genetics; Ion Channels - metabolism; Ion Channels - physiology; line differences; messenger RNA; Metabolic disorders; Metabolic syndrome; Metabolic Syndrome - etiology; Mice; Mice, Inbred C57BL; Mice, Inbred Strains; mitochondria; Mitochondria - metabolism; Mitochondrial Proteins - genetics; Mitochondrial Proteins - metabolism; Mitochondrial Proteins - physiology; Muscles; Muscles - chemistry; Muscles - ultrastructure; Obesity; protein synthesis; Risk; Risk factors; Rodents; Skeletal muscle; Tissues; Uncoupling Protein 1; Up-Regulation - genetics; Weight Gain
• DOI: 10.1073/pnas.0610416104
• ISSN: 0027-8424

C57BL/6 (B6) mice subjected to a high-fat diet develop metabolic syndrome with obesity, hyperglycemia, and insulin resistance, whereas 129S6/SvEvTac (129) mice are relatively protected from this disorder because of differences in higher basal energy expenditure in 129 mice, leading to lower weight gain. At a molecular level, this difference correlates with a marked higher expression of uncoupling protein 1 (UCP1) and a higher degree of uncoupling in vitro in mitochondria isolated from muscle of 129 versus B6 mice. Detailed histological examination, however, reveals that this UCP1 is in mitochondria of brown adipocytes interspersed between muscle bundles. Indeed, the number of UCP1-positive brown fat cells in intermuscular fat in 129 mice is >700-fold higher than in B6 mice. These brown fat cells are subject to further up-regulation of UCP1 after stimulation with a β₃-adrenergic receptor agonist. Thus, ectopic deposits of brown adipose tissue in intermuscular depots with regulatable expression of UCP1 provide a genetically based mechanism of protection from weight gain and metabolic syndrome between strains of mice.