title: Adipose tissue and the insulin resistance syndrome.
abstract: Obesity is associated with insulin resistance. Insulin resistance underlies a constellation of adverse metabolic and physiological changes (the insulin resistance syndrome) which is a strong risk factor for development of type 2 diabetes and CHD. The present article discusses how accumulation of triacylglycerol in adipocytes can lead to deterioration of the responsiveness of glucose metabolism in other tissues. Lipodystrophy, lack of adipose tissue, is also associated with insulin resistance. Any plausible explanation for the link between excess adipose tissue and insulin resistance needs to be able to account for this observation. Adipose tissue in obesity becomes refractory to suppression of fat mobilization by insulin, and also to the normal acute stimulatory effect of insulin on activation of lipoprotein lipase (involved in fat storage). The net effect is as though adipocytes are 'full up' and resisting further fat storage. Thus, in the postprandial period especially, there is an excess flux of circulating lipid metabolites that would normally have been 'absorbed' by adipose tissue. This situation leads to fat deposition in other tissues. Accumulation of triacylglycerol in skeletal muscles and in liver is associated with insulin resistance. In lipodystrophy there is insufficient adipose tissue to absorb the postprandial influx of fatty acids, so these fatty acids will again be directed to other tissues. This view of the link between adipose tissue and insulin resistance emphasises the important role of adipose tissue in 'buffering' the daily influx of dietary fat entering the circulation and preventing excessive exposure of other tissues to this influx.
authors.affiliation: Oxford Centre for Diabetes, Endocrinology and Metabolism, Radcliffe Infirmary, UK. keith.frayn@oxlip.ox.ac.uk
authors.forename: K N
authors.initials: KN
authors.lastname: Frayn
mesh_terms: D000273:Adipose Tissue / Q000201:enzymology / Q000378:metabolism*; D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000209:etiology; D005947:Glucose / Q000378:metabolism; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology; D008060:Lipodystrophy; D008071:Lipoprotein Lipase / Q000378:metabolism; D024821:Metabolic Syndrome / Q000502:physiology*; D009765:Obesity / Q000150:complications / Q000378:metabolism* / Q000503:physiopathology; D014280:Triglycerides / Q000097:blood / Q000378:metabolism*
chemical_list: D014280:Triglycerides; D008071:Lipoprotein Lipase; D005947:Glucose