Insulin resistance and diabetes mellitus in transgenic mice expressing nuclear SREBP-1c in adipose tissue: model for congenital generalized lipodystrophy

Adipose tissue as a buffer for daily lipid flux

“…Human lipodystrophy, whether total or partial, is an insulin-resistant state, often severely so, and is usually associated with Type II diabetes [7]. In rodent models, adipose tissue deficiency is also associated with insulin resistance and diabetes [8,58,64] and again with accumulation of triacylglycerol in skeletal muscle, liver and pancreas [58,65]. These and other observations have led to the concept of 'lipotoxicity' in the pathogenesis of Type II diabetes [66].…”

“…Paradoxically, a deficiency of adipose tissue, as in lipodystrophy or lipoatrophy in humans [6,7] and rodents [8,9,10], is also associated with insulin resistance. These observations suggest that adipose tissue in health is carrying out some active function that maintains normal insulin sensitivity.…”

Triacylglycerol Metabolism In Adipose Tissue

“…While † Author for correspondence, University of California, Department of Nutritional Sciences & Toxicology, Berkeley, CA 94720, USA, adipocyte number has been shown to increase (hyperplasia) in morbid obesity, obesity is primarily attributed to adipocyte hypertrophy that occurs when TAG synthesis (esterification) exceeds TAG breakdown (lipolysis), resulting in elevated TAG storage [1]. Although it has been postulated that large adipocyte size may contribute to insulin resistance, the molecular mechanism is not clear.Paradoxically, the metabolic abnormalities typically found in obesity are also associated with lipodystrophies that are characterized by selective loss of adipose tissue from particular regions of the body [3][4][5][6]. Although the underlying molecular mechanisms are not clear, metabolic complications may result from ectopic storage of TAG in tissues such as the liver and muscle [7][8][9].…”

“…Paradoxically, the metabolic abnormalities typically found in obesity are also associated with lipodystrophies that are characterized by selective loss of adipose tissue from particular regions of the body [3][4][5][6]. Although the underlying molecular mechanisms are not clear, metabolic complications may result from ectopic storage of TAG in tissues such as the liver and muscle [7][8][9].…”

Hepatic adiponectin receptors (ADIPOR) 1 and 2 mRNA and their relation to insulin resistance in obese humans

“…3 Studies in lipodystrophic and obese humans as well as in animal models suggest that adipose tissue (AT) has an important role in IR. [4][5][6] Expansion of AT is associated with pro-inflammatory changes and altered adipokine secretion, thereby affecting the function of distant tissues such as skeletal muscle, liver and vascular cells. [7][8][9] However, clinical experience and well-documented studies in different populations indicate that metabolically benign, insulin-sensitive phenotypes are not infrequent within the obesity spectrum.…”