Enhanced metabolic flexibility associated with elevated adiponectin levels.
Metabolically healthy individuals effectively adapt to changes in nutritional state. Here, we focus on the effects of the adipocyte-derived secretory molecule adiponectin on adipose tissue in mouse models with genetically altered adiponectin levels. We found that higher adiponectin levels increased sensitivity to the lipolytic effects of adrenergic receptor agonists. In parallel, adiponectin-overexpressing mice also display enhanced clearance of circulating fatty acids and increased expansion of subcutaneous adipose tissue with chronic high fat diet (HFD) feeding. These adaptive changes to the HFD were associated with increased mitochondrial density in adipocytes, smaller adipocyte size, and a general transcriptional up-regulation of factors involved in lipid storage through efficient esterification of free fatty acids. The physiological response to adiponectin overexpression resembles in many ways the effects of chronic exposure to beta3-adrenergic agonist treatment, which also results in improvements in insulin sensitivity. In addition, using a novel computed tomography-based method for measurements of hepatic lipids, we resolved the temporal events taking place in the liver in response to acute HFD exposure in both wild-type and adiponectin-overexpressing mice. Increased levels of adiponectin potently protect against HFD-induced hepatic lipid accumulation and preserve insulin sensitivity. Given these profound effects of adiponectin, we propose that adiponectin is a factor that increases the metabolic flexibility of adipose tissue, enhancing its ability to maintain proper function under metabolically challenging conditions.
Asterholm
Ingrid Wernstedt
IW
Touchstone Diabetes Center, Department of Internal Medicine, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390-8549, USA.
Scherer
Philipp E
PE
D052242:Adiponectin / Q000378:metabolism*; D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D019069:Cell Respiration; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D004041:Dietary Fats / Q000008:administration & dosage / Q000494:pharmacology; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005234:Fatty Liver / Q000097:blood / Q000378:metabolism / Q000473:pathology; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D005990:Glycerol / Q000097:blood; D007328:Insulin / Q000097:blood; D008099:Liver / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009929:Organ Size / Q000187:drug effects; D010766:Phosphorylation / Q000187:drug effects; D022702:Receptors, Adrenergic, beta-3 / Q000378:metabolism; D014057:Tomography, X-Ray Computed; D014280:Triglycerides / Q000378:metabolism; D015430:Weight Gain / Q000187:drug effects
D052242:Adiponectin; D001786:Blood Glucose; C492004:Creb1 protein, mouse; D017362:Cyclic AMP Response Element-Binding Protein; D004041:Dietary Fats; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D022702:Receptors, Adrenergic, beta-3; D014280:Triglycerides; D005990:Glycerol