title: Effects of high-fat overfeeding on mitochondrial function, glucose and fat metabolism, and adipokine levels in low-birth-weight subjects.
abstract: Low birth weight (LBW) is associated with an increased risk of insulin resistance and downregulation of oxidative phosphorylation (OXPHOS) genes when exposed to a metabolic challenge of high-fat overfeeding (HFO). To elaborate further on the differential effects of HFO in LBW subjects, we measured in vivo mitochondrial function, insulin secretion, hepatic glucose production, and plasma levels of key regulatory hormones before and after 5 days of HFO in 20 young LBW and 26 normal-birth-weight (NBW) men. The LBW subjects developed peripheral insulin resistance after HFO due to impaired endogenous glucose storage (9.42 ± 4.19 vs. 5.91 ± 4.42 mg·kg FFM(-1)·min(-1), P = 0.01). Resting muscle phosphorcreatine and total ATP in muscle increased significantly after HFO in LBW subjects only, whereas additional measurements of mitochondrial function remained unaffected. Despite similar plasma FFA levels, LBW subjects displayed increased fat oxidation during insulin infusion compared with normal-birth-weight (NBW) subjects after HFO (0.37 ± 0.35 vs. 0.17 ± 0.33 mg·kg FFM(-1)·min(-1), P = 0.02). In contrast to NBW subjects, the plasma leptin levels of LBW subjects did not increase, and the plasma gastric inhibitory polypeptide (GIP) as well as pancreatic polypeptide (PP) levels increased less in LBW compared with NBW subjects during HFO. In conclusion, HFO unmasks dissociation between insulin resistance and mitochondrial dysfunction in LBW subjects, suggesting that insulin resistance may be a cause, rather than an effect, of impaired muscle OXPHOS gene expression and mitochondrial dysfunction. Reduced increments in response to HFO of fasting plasma leptin, PP, and GIP levels may contribute to insulin resistance, lower satiety, and impaired insulin secretion in LBW subjects.
authors.affiliation: Steno Diabetes Center, Niels Steensens Vej 1, Gentofte, Denmark. charlotte.broens@rh.regionh.dk
authors.forename: Charlotte
authors.initials: C
authors.lastname: Brøns
authors.forename: Stine
authors.initials: S
authors.lastname: Jacobsen
authors.forename: Natalie
authors.initials: N
authors.lastname: Hiscock
authors.forename: Andrew
authors.initials: A
authors.lastname: White
authors.forename: Emma
authors.initials: E
authors.lastname: Nilsson
authors.forename: David
authors.initials: D
authors.lastname: Dunger
authors.forename: Arne
authors.initials: A
authors.lastname: Astrup
authors.forename: Bjørn
authors.initials: B
authors.lastname: Quistorff
authors.forename: Allan
authors.initials: A
authors.lastname: Vaag
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D054392:Adipokines / Q000097:blood*; D000328:Adult; D018592:Cross-Over Studies; D003718:Denmark / Q000453:epidemiology; D003924:Diabetes Mellitus, Type 2 / Q000209:etiology; D004041:Dietary Fats / Q000009:adverse effects*; D005749:Gastric Inhibitory Polypeptide / Q000097:blood; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D007230:Infant, Low Birth Weight; D007231:Infant, Newborn; D007333:Insulin Resistance; D020738:Leptin / Q000097:blood; D050356:Lipid Metabolism; D008297:Male; D008931:Mitochondria, Muscle / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism; D010191:Pancreatic Polypeptide / Q000097:blood; D010725:Phosphocreatine / Q000378:metabolism; D011498:Protein Precursors / Q000097:blood; D012042:Registries; D055815:Young Adult
chemical_list: D054392:Adipokines; D004041:Dietary Fats; D020738:Leptin; C043710:PPY protein, human; D011498:Protein Precursors; D010725:Phosphocreatine; D005749:Gastric Inhibitory Polypeptide; D010191:Pancreatic Polypeptide; D000255:Adenosine Triphosphate; D005947:Glucose