Ermina Bach1, Andreas B Møller2, Jens O L Jørgensen2, Mikkel H Vendelbo3, Niels Jessen2, Steen B Pedersen2, Thomas S Nielsen4, Niels Møller2. 1. Medical Research LaboratoriesDepartment of Clinical Medicine, Incuba/Skejby, Aarhus N, Denmark Department of Endocrinology and Internal Medicine Bach.Ermina@gmail.com. 2. Medical Research LaboratoriesDepartment of Clinical Medicine, Incuba/Skejby, Aarhus N, Denmark Department of Endocrinology and Internal Medicine. 3. Medical Research LaboratoriesDepartment of Clinical Medicine, Incuba/Skejby, Aarhus N, Denmark Department of Nuclear Medicine & PET-CentreAarhus University Hospital, Aarhus C, Denmark. 4. Medical Research LaboratoriesDepartment of Clinical Medicine, Incuba/Skejby, Aarhus N, Denmark Department of Endocrinology and Internal Medicine The Novo Nordisk Foundation Centre for Basic Metabolic ResearchSection on Integrative Physiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Abstract
OBJECTIVE: Acute and chronic inflammatory and metabolic responses are generated by lipopolysaccharide (LPS) during acute illness and in the pathogenesis of the metabolic syndrome, type 2 diabetes and cardiovascular disease, but whether these responses depend on intact pituitary release of hormones are not clearly identified. We compared the metabolic effects of LPS in hypopituitary patients (HPs) (in the absence of growth hormone (GH) and ACTH responses) and healthy control subjects (CTR) (with normal pituitary hormone responses). DESIGN: Single-blind randomized. METHODS: We compared the effects of LPS on glucose, protein and lipid metabolism in eight HP and eight matched CTR twice during 4-h basal and 2-h hyperinsulinemic-euglycemic clamp conditions with muscle and fat biopsies in each period during infusion with saline or LPS. RESULTS:LPS increased cortisol and GH levels in CTR but not in HP. Also, it increased whole-body palmitate fluxes (3-fold) and decreased palmitate-specific activity (SA) 40-50% in CTR, but not in HP. G(0)/G(1) Switch Gene 2 (G0S2 - an inhibitor of lipolysis) adipose tissue (AT) mRNA was decreased in CTR. Although LPS increased phenylalanine fluxes significantly more in CTR, there was no difference in glucose metabolism between groups and intramyocellular insulin signaling was unaltered in both groups. CONCLUSIONS:LPS increased indices of lipolysis and amino acid/protein fluxes significantly more in CTR compared with HP and decreased adipocyte G0S2 mRNA only in CTR. Thus, in humans intact pituitary function and appropriate cortisol and GH release are crucial components of the metabolic response to LPS.
RCT Entities:
OBJECTIVE: Acute and chronic inflammatory and metabolic responses are generated by lipopolysaccharide (LPS) during acute illness and in the pathogenesis of the metabolic syndrome, type 2 diabetes and cardiovascular disease, but whether these responses depend on intact pituitary release of hormones are not clearly identified. We compared the metabolic effects of LPS in hypopituitary patients (HPs) (in the absence of growth hormone (GH) and ACTH responses) and healthy control subjects (CTR) (with normal pituitary hormone responses). DESIGN: Single-blind randomized. METHODS: We compared the effects of LPS on glucose, protein and lipid metabolism in eight HP and eight matched CTR twice during 4-h basal and 2-h hyperinsulinemic-euglycemic clamp conditions with muscle and fat biopsies in each period during infusion with saline or LPS. RESULTS:LPS increased cortisol and GH levels in CTR but not in HP. Also, it increased whole-body palmitate fluxes (3-fold) and decreased palmitate-specific activity (SA) 40-50% in CTR, but not in HP. G(0)/G(1) Switch Gene 2 (G0S2 - an inhibitor of lipolysis) adipose tissue (AT) mRNA was decreased in CTR. Although LPS increased phenylalanine fluxes significantly more in CTR, there was no difference in glucose metabolism between groups and intramyocellular insulin signaling was unaltered in both groups. CONCLUSIONS:LPS increased indices of lipolysis and amino acid/protein fluxes significantly more in CTR compared with HP and decreased adipocyte G0S2 mRNA only in CTR. Thus, in humans intact pituitary function and appropriate cortisol and GH release are crucial components of the metabolic response to LPS.
Authors: Astrid Johannesson Hjelholt; Kevin Y Lee; Mai Christiansen Arlien-Søborg; Steen Bønløkke Pedersen; John J Kopchick; Vishwajeet Puri; Niels Jessen; Jens Otto L Jørgensen Journal: Mol Metab Date: 2019-08-20 Impact factor: 7.422