TY - JOUR
T1 - Adipose tissue as an endocrine organ
T2 - Implications of its distribution on free fatty acid metabolism
AU - Jensen, Michael D.
N1 - Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2006/5
Y1 - 2006/5
N2 - Free fatty acids (FFAs) are the main circulating lipid fuel in the post-absorptive state. Elevated plasma FFA concentrations are associated with increased endogenous glucose production rates and insulin resistance in skeletal muscle, whereas long-term exposure of pancreatic β-cells to elevated FFA impairs insulin secretion, with a consequently increased risk of developing type 2 diabetes. A range of adverse changes occur in the vascular endothelium in response to elevation of plasma FFA concentrations that are similar to key early steps in atherogenesis. These include reduced endothelium-dependent vasodilatation and increased expression of adhesion molecules. We have found that the majority of systemic plasma FFAs originate from upper-body subcutaneous fat, with lesser contributions from leg fat and intra-abdominal adipocytes, even in persons with abdominal obesity. However, systemic FFA concentrations correlate positively with visceral fat, so that FFA release from visceral depots appears to serve as a marker of systemic insulin resistance. In addition, the secretion of a range of bioactive substances from intra-abdominal adipocytes (adipokines) is disturbed, with potentially deleterious consequences for metabolism and overall cardiometabolic risk. Interventions that reduce circulating FFA, either due to or independently of weight loss, are likely to improve insulin sensitivity, β-cell function, and cardiovascular risk. Weight loss in overweight or obese patients would have the additional benefit of reducing intra-abdominal adiposity and tending to correct the pathologically altered adipokine secretion associated with abdominal obesity.
AB - Free fatty acids (FFAs) are the main circulating lipid fuel in the post-absorptive state. Elevated plasma FFA concentrations are associated with increased endogenous glucose production rates and insulin resistance in skeletal muscle, whereas long-term exposure of pancreatic β-cells to elevated FFA impairs insulin secretion, with a consequently increased risk of developing type 2 diabetes. A range of adverse changes occur in the vascular endothelium in response to elevation of plasma FFA concentrations that are similar to key early steps in atherogenesis. These include reduced endothelium-dependent vasodilatation and increased expression of adhesion molecules. We have found that the majority of systemic plasma FFAs originate from upper-body subcutaneous fat, with lesser contributions from leg fat and intra-abdominal adipocytes, even in persons with abdominal obesity. However, systemic FFA concentrations correlate positively with visceral fat, so that FFA release from visceral depots appears to serve as a marker of systemic insulin resistance. In addition, the secretion of a range of bioactive substances from intra-abdominal adipocytes (adipokines) is disturbed, with potentially deleterious consequences for metabolism and overall cardiometabolic risk. Interventions that reduce circulating FFA, either due to or independently of weight loss, are likely to improve insulin sensitivity, β-cell function, and cardiovascular risk. Weight loss in overweight or obese patients would have the additional benefit of reducing intra-abdominal adiposity and tending to correct the pathologically altered adipokine secretion associated with abdominal obesity.
KW - Abdominal obesity
KW - Cardiovascular risk
KW - Dyslipidaemia
KW - Free fatty acids
KW - Insulin resistance
KW - Lipolysis
UR - http://www.scopus.com/inward/record.url?scp=33749038908&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33749038908&partnerID=8YFLogxK
U2 - 10.1093/eurheartj/sul003
DO - 10.1093/eurheartj/sul003
M3 - Article
AN - SCOPUS:33749038908
SN - 1520-765X
VL - 8
SP - B13-B19
JO - European Heart Journal, Supplement
JF - European Heart Journal, Supplement
IS - B
ER -