title: Abdominal obesity: role in the pathophysiology of metabolic disease and cardiovascular risk.
abstract: Visceral adiposity has been identified as an independent risk factor for cardiovascular disease and the so-called metabolic syndrome. The canine obesity model closely recapitulates the correlation between human visceral adiposity and insulin resistance. A recent canine study indicates that insulin expands the volume of distribution associated with skeletal muscle, and that its ability to enhance macromolecular distribution within this space is blunted in the fat-fed obese canine model. Our canine study supports the portal theory of insulin resistance, in which free fatty acids (FFAs) from visceral fat directly enter the liver and have a detrimental effect on insulin action. The role of adipokines in this condition remains less clear. Sympathetic nervous system hyperactivity in obesity may also contribute to excessive FFA release, hypertension, and insulin resistance. Pathologies interrelated with insulin resistance include beta-cell hypersecretion, reduced insulin clearance, and resultant hyperinsulinemia. An observed nocturnal increase in plasma FFA levels may account for both insulin resistance and compensatory hyperinsulinemia and warrants further investigation. The elucidation of these interrelated pathologies may help reveal points where medical intervention can reduce metabolic disease.
authors.affiliation: Department of Physiology and Biophysics, Keck School of Medicine, University of Southern California, Los Angeles, California 90033, USA. rbergman@usc.edu
authors.forename: Richard N
authors.initials: RN
authors.lastname: Bergman
authors.forename: Stella P
authors.initials: SP
authors.lastname: Kim
authors.forename: Isabel R
authors.initials: IR
authors.lastname: Hsu
authors.forename: Karyn J
authors.initials: KJ
authors.lastname: Catalano
authors.forename: Jenny D
authors.initials: JD
authors.lastname: Chiu
authors.forename: Morvarid
authors.initials: M
authors.lastname: Kabir
authors.forename: Joyce M
authors.initials: JM
authors.lastname: Richey
authors.forename: Marilyn
authors.initials: M
authors.lastname: Ader
mesh_terms: D000818:Animals; D002318:Cardiovascular Diseases / Q000503:physiopathology*; D004195:Disease Models, Animal; D004285:Dogs; D005230:Fatty Acids, Nonesterified / Q000502:physiology; D006943:Hyperglycemia / Q000503:physiopathology; D006946:Hyperinsulinism / Q000503:physiopathology; D007333:Insulin Resistance / Q000502:physiology*; D050417:Insulin-Secreting Cells / Q000502:physiology; D050152:Intra-Abdominal Fat / Q000503:physiopathology*; D024821:Metabolic Syndrome / Q000209:etiology / Q000503:physiopathology*; D012307:Risk Factors
chemical_list: D005230:Fatty Acids, Nonesterified