Fritsch 2015 Am J Clin Nutr
|Fritsch M, Koliaki C, Livingstone R, Phielix E, Bierwagen A, Meisinger M, Jelenik T, Strassburger K, Zimmermann S, Brockmann K, Wolff C, Hwang JH, Szendroedi J, Roden M (2015) Time course of postprandial hepatic phosphorus metabolites in lean, obese, and type 2 diabetes patients. Am J Clin Nutr 102:1051-8.|
Abstract: Impaired energy metabolism is a possible mechanism that contributes to insulin resistance and ectopic fat storage.
We examined whether meal ingestion differently affects hepatic phosphorus metabolites in insulin-sensitive and insulin-resistant humans.
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 γATP, inorganic phosphate (Pi), and the fat content [hepatocellular lipids (HCLs)] with the use of (31)P/(1)H 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.
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 γATP concentrations, the maximum postprandial increase of γATP 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.
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.
This trial was registered at clinicaltrials.gov as NCT01229059.
© 2015 American Society for Nutrition.
• Keywords: Hepatic steatosis, Mitochondrial function, Mixed-meal test, Phosphorus magnetic resonance spectroscopy, Type 2 diabetes
• O2k-Network Lab: DE Duesseldorf Roden M
Labels: MiParea: Respiration, Exercise physiology;nutrition;life style, Patients Pathology: Diabetes, Obesity
Organism: Human Tissue;cell: Skeletal muscle
Coupling state: OXPHOS, ET Pathway: N, NS HRR: Oxygraph-2k