期刊
AMERICAN JOURNAL OF CLINICAL NUTRITION
卷 102, 期 5, 页码 1051-1058出版社
OXFORD UNIV PRESS
DOI: 10.3945/ajcn.115.107599
关键词
hepatic steatosis; mitochondrial function; mixed-meal test; phosphorus magnetic resonance spectroscopy; type 2 diabetes
资金
- Ministry of Science and Research of the State of North Rhine-Westphalia
- German Federal Ministry of Health
- Federal Ministry for Research
- European Foundation for the Study of Diabetes
- Helmholtz Alliance Imaging and Curing Environmental Metabolic Diseases
- Schmutzler Stiftung
- German Research Foundation [SFB1116]
- European Society of Paediatric Endocrinology research fellowship - Novo Nordisk A/S
Background: Impaired energy metabolism is a possible mechanism that contributes to insulin resistance and ectopic fat storage. Objective: We examined whether meal ingestion differently affects hepatic phosphorus metabolites in insulin-sensitive and insulin-resistant humans. Design: Young, lean, insulin-sensitive humans (CONs) [mean +/- SD body mass index (BMI; in kg/m(2)): 23.2 +/- 1.5]; insulin-resistant, glucose-tolerant, obese humans (OBEs) (BMI: 34.3 +/- 1.7); and type 2 diabetes patients (T2Ds) (BMI: 32.0 +/- 2.4) were studied (n = 10/group). T2Ds (61 +/- 7 y old) were older (P < 0.001) than were OBEs (31 7 y old) and CONs (28 +/- 3 y old). We quantified hepatic gamma ATP, inorganic phosphate (Pi), and the fat content [hepatocellular lipids (HCLs)] with the use of P-31/H-1 magnetic resonance spectroscopy before and at 160 and 240 min after a high-caloric mixed meal. In a subset of volunteers, we measured the skeletal muscle oxidative capacity with the use of high-resolution respirometry. Whole-body insulin sensitivity (M value) was assessed with the use of hyperinsulinemic-euglycemic clamps. Results: OBEs and T2Ds were similarly insulin resistant (M value: 3.5 +/- 1.4 and 1.9 +/- 2.5 mg.kg(-1).min(-1), respectively; P = 0.9) and had 12-fold (P = 0.01) and 17-fold (P = 0.002) higher HCLs, respectively, than those of lean persons. Despite comparable fasting hepatic gamma ATP concentrations, the maximum postprandial increase of gamma ATP was 6-fold higher in OBEs (0.7 +/- 0.2 mmol/L; P = 0.03) but only tended to be higher in T2Ds (0.6 +/- 0.2 mmol/L; P = 0.09) than in CONs (0.1 +/- 0.1 mmol/L). However, in the fasted state, muscle complex I activity was 53% lower (P = 0.01) in T2Ds but not in OBEs (P = 0.15) than in CONs. Conclusions: Young, obese, nondiabetic humans exhibit augmented postprandial hepatic energy metabolism, whereas elderly T2Ds have impaired fasting muscle energy metabolism. These findings support the concept of a differential and tissue-specific regulation of energy metabolism, which can occur independently of insulin resistance.
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