title: Middle-aged overweight South Asian men exhibit a different metabolic adaptation to short-term energy restriction compared with Europeans.
abstract: OBJECTIVE
  South Asians have a higher risk of developing type 2 diabetes than Europeans. The underlying cause of this excess risk is still poorly understood but might be related to differences in the regulation of energy/nutrient-sensing pathways in metabolic tissues and subsequent changes in whole-body substrate metabolism. In this study, we investigated the whole-body and skeletal muscle metabolic adaptations to short-term energy restriction in South Asian and European volunteers.
  
  
  METHODS
  Twenty-four middle-aged overweight South Asian and European men underwent a two-step hyperinsulinaemic-euglycaemic clamp, with skeletal muscle biopsies and indirect calorimetry before and after an 8 day diet very low in energy (very low calorie diet [VLCD]). Abdominal fat distribution and hepatic triacylglycerol content were assessed using MRI and MR spectroscopy.
  
  
  RESULTS
  South Asian men had higher hepatic triacylglycerol content than European men, and exhibited elevated clamp insulin levels that probably reflect a lower insulin clearance rate. Despite higher insulin levels, endogenous glucose production rate was similar and glucose disposal rate (Rd) and nonoxidative glucose disposal rate (NOGD) were significantly lower in South Asian than European men, indicating impaired whole-body insulin sensitivity. Energy restriction decreased abdominal fat mass and hepatic triacylglycerol content in both groups. However, the shift induced by energy restriction from glucose towards lipid oxidation observed in European men was impaired in South Asian men, indicating whole-body metabolic inflexibility. Remarkably, although energy restriction improved hepatic insulin sensitivity in both groups, Rd improved only in South Asian men owing to higher NOGD. At the molecular level, an increase in insulin-induced activation of the skeletal muscle mTOR pathway was found in South Asian men, showing that skeletal muscle energy/nutrient-sensing pathways were differentially affected by energy restriction.
  
  
  CONCLUSIONS
  We conclude that South Asian men exhibit a different metabolic adaptation to short-term energy restriction than European men.
  
  
  BACKGROUND
  Dutch trial registry ( www.trialregister.nl ), trial number NTR 2473.
authors.affiliation: Department of Endocrinology, Leiden University Medical Centre, PO Box 9600, 2300 RC, Leiden, the Netherlands, l.e.h.bakker@lumc.nl.
authors.forename: Leontine E H
authors.initials: LE
authors.lastname: Bakker
authors.forename: Bruno
authors.initials: B
authors.lastname: Guigas
authors.forename: Linda D
authors.initials: LD
authors.lastname: van Schinkel
authors.forename: Gerard C M
authors.initials: GC
authors.lastname: van der Zon
authors.forename: Trea C M
authors.initials: TC
authors.lastname: Streefland
authors.forename: Jan B
authors.initials: JB
authors.lastname: van Klinken
authors.forename: Jacqueline T
authors.initials: JT
authors.lastname: Jonker
authors.forename: Hildo J
authors.initials: HJ
authors.lastname: Lamb
authors.forename: Johannes W A
authors.initials: JW
authors.lastname: Smit
authors.forename: Hanno
authors.initials: H
authors.lastname: Pijl
authors.forename: A Edo
authors.initials: AE
authors.lastname: Meinders
authors.forename: Ingrid M
authors.initials: IM
authors.lastname: Jazet
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D000222:Adaptation, Physiological / Q000502:physiology*; D000328:Adult; D001208:Asia / Q000208:ethnology; D044466:Asian People; D031204:Caloric Restriction / Q000208:ethnology; D006801:Humans; D050356:Lipid Metabolism; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000378:metabolism; D009426:Netherlands; D050177:Overweight / Q000178:diet therapy* / Q000208:ethnology* / Q000378:metabolism*; D015398:Signal Transduction; D044465:White People
chemical_list: D055372:AMP-Activated Protein Kinases