TY - JOUR

T1 - Stress hormone release is a key component of the metabolic response to lipopolysaccharide (LPS)

T2 - studies in hypopituitary and healthy subjects

AU - Bach, Ermina

AU - Møller, Andreas Buch

AU - Jorgensen, Jens Otto L

AU - Vendelbo, Mikkel Holm

AU - Jessen, Niels

AU - Pedersen, Steen Bønløkke

AU - Nielsen, Thomas Svava

AU - Møller, Niels

PY - 2016/8/25

Y1 - 2016/8/25

N2 - OBJECTIVE: Lipopolysaccharide (LPS) generates acute and chronic inflammatory and metabolic responses during acute illness and in the pathogenesis of the metabolic syndrome, type 2 diabetes and cardiovascular disease, but it is unclear whether these responses depend on intact pituitary release of stress hormones. We compared the metabolic effects of LPS in hypopituitary patients (HP) (in the absence of pituitary stress hormone responses) and healthy control subjects (CTR) (with normal pituitary stress hormone responses).DESIGN: Single blind randomized.METHODS: We compared 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 biopsies and fat biopsies in each period during infusion with saline or LPS.RESULTS: LPS increased cortisol and growth hormone (GH) levels in CTR but not in HP. LPS increased whole body palmitate fluxes (3-fold) and decreased palmitate specific activity 40-50 % in CTR, but not in HP. G(0)/G(1) Switch Gene 2 (G0S2 - an inhibitor of lipolysis) adipose tissue mRNA was decreased in CTR. LPS increased phenylalanine fluxes significantly more in CTR, whereas there was no difference in glucose metabolism between groups and intramyocellular insulin signalling was unaltered in both groups.CONCLUSIONS: LPS increased indices of lipolysis and amino acid/protein fluxes significantly more in CTR compared to 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.

AB - OBJECTIVE: Lipopolysaccharide (LPS) generates acute and chronic inflammatory and metabolic responses during acute illness and in the pathogenesis of the metabolic syndrome, type 2 diabetes and cardiovascular disease, but it is unclear whether these responses depend on intact pituitary release of stress hormones. We compared the metabolic effects of LPS in hypopituitary patients (HP) (in the absence of pituitary stress hormone responses) and healthy control subjects (CTR) (with normal pituitary stress hormone responses).DESIGN: Single blind randomized.METHODS: We compared 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 biopsies and fat biopsies in each period during infusion with saline or LPS.RESULTS: LPS increased cortisol and growth hormone (GH) levels in CTR but not in HP. LPS increased whole body palmitate fluxes (3-fold) and decreased palmitate specific activity 40-50 % in CTR, but not in HP. G(0)/G(1) Switch Gene 2 (G0S2 - an inhibitor of lipolysis) adipose tissue mRNA was decreased in CTR. LPS increased phenylalanine fluxes significantly more in CTR, whereas there was no difference in glucose metabolism between groups and intramyocellular insulin signalling was unaltered in both groups.CONCLUSIONS: LPS increased indices of lipolysis and amino acid/protein fluxes significantly more in CTR compared to 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.

U2 - 10.1530/EJE-16-0444

DO - 10.1530/EJE-16-0444

M3 - Journal article

C2 - 27562403

VL - 175

SP - 455

EP - 465

JO - European Journal of Endocrinology

JF - European Journal of Endocrinology

SN - 0804-4643

IS - 5

ER -