title: In vivo 2H2O administration reveals impaired triglyceride storage in adipose tissue of insulin-resistant humans.
abstract: Indirect evidence suggests that impaired triglyceride storage in the subcutaneous fat depot contributes to the development of insulin resistance via lipotoxicity. We directly tested this hypothesis by measuring, in vivo, TG synthesis, de novo lipogenesis (DNL), adipocyte proliferation, and insulin suppression of lipolysis in subcutaneous adipose tissue of BMI-matched individuals classified as insulin resistant (IR) or insulin sensitive (IS). Nondiabetic, moderately obese subjects with BMI 25-35 kg/m(2), classified as IR or IS by the modified insulin suppression test, consumed deuterated water ((2)H2O) for 4 weeks. Deuterium incorporation into glycerol, palmitate, and DNA indicated TG synthesis, DNL, and adipocyte proliferation, respectively. Net TG synthesis and DNL in adipose cells were significantly lower in IR as compared with IS subjects, whereas adipocyte proliferation did not differ significantly. Plasma FFAs measured during an insulin suppression test were 2.5-fold higher in IR subjects, indicating resistance to insulin suppression of lipolysis. Adipose TG synthesis correlated directly with DNL but not with proliferation. These results provide direct in vivo evidence for impaired TG storage in subcutaneous adipose tissue of IR as compared with IS. Relative inability to store TG in the subcutaneous depot may represent a mechanism contributing to the development of insulin resistance in the setting of obesity.
authors.affiliation: Department of Nutritional Science and Toxicology, University of California at Berkeley, Berkeley, CA.
authors.forename: Candice A
authors.initials: CA
authors.lastname: Allister
authors.affiliation: Department of Medicine, Stanford University School of Medicine, Stanford, CA.
authors.forename: Li-fen
authors.initials: LF
authors.lastname: Liu
authors.affiliation: Department of Medicine, Stanford University School of Medicine, Stanford, CA.
authors.forename: Cindy A
authors.initials: CA
authors.lastname: Lamendola
authors.affiliation: Department of Medicine, Stanford University School of Medicine, Stanford, CA.
authors.forename: Colleen M
authors.initials: CM
authors.lastname: Craig
authors.affiliation: Diabetes, Endocrinology, and Obesity Branch, National Institute of Digestive Diseases and Kidney Disease, National Institutes of Health, Bethesda, MD.
authors.forename: Samuel W
authors.initials: SW
authors.lastname: Cushman
authors.affiliation: Department of Nutritional Science and Toxicology, University of California at Berkeley, Berkeley, CA.
authors.forename: Marc K
authors.initials: MK
authors.lastname: Hellerstein
authors.affiliation: Department of Medicine, Stanford University School of Medicine, Stanford, CA.
authors.forename: Tracey L
authors.initials: TL
authors.lastname: McLaughlin
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism*; D015992:Body Mass Index; D017666:Deuterium Oxide / Q000378:metabolism*; D005260:Female; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology*; D008066:Lipolysis / Q000502:physiology; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000378:metabolism; D014280:Triglycerides / Q000378:metabolism*
chemical_list: D014280:Triglycerides; D017666:Deuterium Oxide
keywords: de novo; insulin resistance; lipogenesis; lipolysis; obesity; subcutaneous adipose; triglycerides