Tumor necrosis factor α −238G>A genotype alters postprandial plasma levels of free fatty acids in obese individuals with type 2 diabetes mellitus

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• 作者：Bé ; né ; dicte Fontaine-Bisson ; Thomas M.S. Wolever ; Jean-Louis Chiasson ; Ré ; mi Rabasa-Lhoret ; Pierre Maheux ; Robert G. Josse ; Lawrence A. Leiter ; N. Wilson Rodger ; Edmond A. Ryan ; Ahmed El-
• 关键词：peanut ; Δ ; ¹² fatty acid desaturase ; prokaryotical expression ; function identification
• 刊名：Metabolism
• 出版年：2007
• 出版时间：May 2007
• 年：2007
• 卷：56
• 期：5
• 页码：649-655
• 全文大小：165 K

文摘

Tumor necrosis factor α (TNF-α) is a proinflammatory cytokine that impairs insulin action and alters lipid metabolism. We investigated the effects of genetic polymorphisms of TNF-α on circulating biomarkers of insulin resistance and lipid metabolism during an 8-hour metabolic profile test and a 2-hour oral glucose tolerance test in subjects with type 2 diabetes mellitus. Subjects (N = 123) recruited were type 2 diabetic men (n = 56) and women (n = 67) aged 36 to 75 years with a body mass index of at least 25 kg/m². Blood samples were collected to determine postprandial changes in circulating lipid levels and biomarkers of insulin resistance. Subjects were genotyped by polymerase chain reaction-restriction fragment length polymorphism for the TNF-α −238G>A, −308G>A, and −863C>A polymorphisms. Compared with subjects who were homozygous for the −238G allele, carriers of the −238A allele had an altered ability to suppress postprandial free fatty acids as shown by an increased net incremental area under the curve (0.26 ± 2.44 vs −1.33 ± 2.71 mEq h⁻¹ L⁻¹, P = .002) during the 8-hour metabolic profile test. This effect was observed in obese (1.04 ± 2.42 vs −1.68 ± 2.70 mEq h⁻¹ L⁻¹, P = .0004) but not in non-obese (−0.63 ± 2.20 vs −0.95 ± 2.71 mEq h⁻¹ L⁻¹, P = .6) individuals. Among obese subjects, carriers of the −308A allele had greater insulin resistance as estimated by the homeostasis model assessment of insulin resistance index (4.36 ± 2.83 vs 2.85 ± 1.75, P = .01), but no differences were observed among non-obese subjects (2.19 ± 1.24 vs 1.97 ± 0.90, P = .6). Our findings suggest that the −238G>A and −308G>A polymorphisms of TNF-α alter circulating free fatty acids and insulin resistance in obese subjects with type 2 diabetes mellitus.