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Effects of high-fat overfeeding on mitochondrial function, glucose and fat metabolism, and adipokine levels in low-birth-weight subjects.
Am J Physiol Endocrinol Metab. 2012 Jan 01; 302(1):E43-51.AJ

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+Show Affiliations

Steno Diabetes Center, Niels Steensens Vej 1, Gentofte, Denmark. charlotte.broens@rh.regionh.dkNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Clinical Trial
Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

21917634

Citation

Brøns, Charlotte, et al. "Effects of High-fat Overfeeding On Mitochondrial Function, Glucose and Fat Metabolism, and Adipokine Levels in Low-birth-weight Subjects." American Journal of Physiology. Endocrinology and Metabolism, vol. 302, no. 1, 2012, pp. E43-51.
Brøns C, Jacobsen S, Hiscock N, et al. Effects of high-fat overfeeding on mitochondrial function, glucose and fat metabolism, and adipokine levels in low-birth-weight subjects. Am J Physiol Endocrinol Metab. 2012;302(1):E43-51.
Brøns, C., Jacobsen, S., Hiscock, N., White, A., Nilsson, E., Dunger, D., Astrup, A., Quistorff, B., & Vaag, A. (2012). Effects of high-fat overfeeding on mitochondrial function, glucose and fat metabolism, and adipokine levels in low-birth-weight subjects. American Journal of Physiology. Endocrinology and Metabolism, 302(1), E43-51. https://doi.org/10.1152/ajpendo.00095.2011
Brøns C, et al. Effects of High-fat Overfeeding On Mitochondrial Function, Glucose and Fat Metabolism, and Adipokine Levels in Low-birth-weight Subjects. Am J Physiol Endocrinol Metab. 2012 Jan 1;302(1):E43-51. PubMed PMID: 21917634.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effects of high-fat overfeeding on mitochondrial function, glucose and fat metabolism, and adipokine levels in low-birth-weight subjects. AU - Brøns,Charlotte, AU - Jacobsen,Stine, AU - Hiscock,Natalie, AU - White,Andrew, AU - Nilsson,Emma, AU - Dunger,David, AU - Astrup,Arne, AU - Quistorff,Bjørn, AU - Vaag,Allan, Y1 - 2011/09/13/ PY - 2011/9/16/entrez PY - 2011/9/16/pubmed PY - 2012/2/15/medline SP - E43 EP - 51 JF - American journal of physiology. Endocrinology and metabolism JO - Am J Physiol Endocrinol Metab VL - 302 IS - 1 N2 - 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. SN - 1522-1555 UR - https://www.unboundmedicine.com/medline/citation/21917634/Effects_of_high_fat_overfeeding_on_mitochondrial_function_glucose_and_fat_metabolism_and_adipokine_levels_in_low_birth_weight_subjects_ L2 - https://journals.physiology.org/doi/10.1152/ajpendo.00095.2011?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -