Intact Pituitary Function is Decisive for the Catabolic Response to TNF-α: Studies of Protein, Glucose and Fatty Acid Metabolism in Hypopituitary and Healthy Subjects

Ermina Bach; Andreas B Møller; Jens O L Jørgensen; Mikkel H Vendelbo; Niels Jessen; Jonas F Olesen; Steen B Pedersen; Thomas Svava Nielsen; Niels Møller

doi:10.1210/jc.2014-2489

Intact Pituitary Function is Decisive for the Catabolic Response to TNF-α: Studies of Protein, Glucose and Fatty Acid Metabolism in Hypopituitary and Healthy Subjects

Ermina Bach, Andreas B Møller, Jens O L Jørgensen, Mikkel H Vendelbo, Niels Jessen, Jonas F Olesen, Steen B Pedersen, Thomas Svava Nielsen, Niels Møller

4 Citations (Scopus)

Abstract

Context: TNF-α generates inflammatory responses and insulin resistance, lipolysis, and protein breakdown. It is unclear whether these changes depend on intact hypothalamo-pituitary stress hormone responses to trigger the release of cortisol and growth hormone. Objective: To define differential effects of TNF-α on glucose, protein, and lipid metabolism in hypopituitary patients (without intact hypothalamo-pituitary axis) and healthy controls. Design: Randomized, placebo controlled, single-blinded. Setting, Participants, and Intervention: We studied eight hypopituitary (HP) patients and eight matched control subjects [control volunteers (CTR)] twice during 4-h basal and 2-h hyperinsulinemic clamp conditions with isotope dilution during infusion of saline or TNF-α(12 ng/kg/h) for 6 h. Main Outcome Measures: Phenylalanine, urea, palmitate, and glucose fluxes and fat biopsies in basal and clamp periods. Results: TNF-α infusion significantly increased cortisol and GH levels in CTR but not in HP. TNF-α increased phenylalanine fluxes in both groups, with the increase being significantly greater in CTR, and raised urea flux by 40 % in CTR without any alteration in HP. Endogenous glucose production (EGP) was elevated in CTR compared to HP after TNF-α administration, whereas insulin sensitivity remained similarly unaffected in both groups. TNF-α increased whole body palmitate fluxes and decreased palmitate specific activity in CTR, but not in HP without statistical difference between groups. We did not detect significant effects TNF-α on lipase expression or regulation in fat. Conclusions: TNF-α increased both urea and amino acid fluxes and EGP significantly more in CTR compared to HP, suggesting that increases in endogenous cortisol and GH release are significant components of the metabolic response to TNF-α.

Original language	English
Journal	The Journal of clinical endocrinology and metabolism
Volume	100
Issue number	2
Pages (from-to)	578-86
Number of pages	9
ISSN	0021-972X
DOIs	https://doi.org/10.1210/jc.2014-2489
Publication status	Published - 1 Feb 2015

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Bach, E., Møller, A. B., Jørgensen, J. O. L., Vendelbo, M. H., Jessen, N., Olesen, J. F., Pedersen, S. B., Nielsen, T. S., & Møller, N. (2015). Intact Pituitary Function is Decisive for the Catabolic Response to TNF-α: Studies of Protein, Glucose and Fatty Acid Metabolism in Hypopituitary and Healthy Subjects. The Journal of clinical endocrinology and metabolism, 100(2), 578-86. https://doi.org/10.1210/jc.2014-2489

Intact Pituitary Function is Decisive for the Catabolic Response to TNF-α: Studies of Protein, Glucose and Fatty Acid Metabolism in Hypopituitary and Healthy Subjects. / Bach, Ermina; Møller, Andreas B; Jørgensen, Jens O L et al.
In: The Journal of clinical endocrinology and metabolism, Vol. 100, No. 2, 01.02.2015, p. 578-86.

Research output: Contribution to journal › Journal article › Research › peer-review

Bach, E, Møller, AB, Jørgensen, JOL, Vendelbo, MH, Jessen, N, Olesen, JF, Pedersen, SB, Nielsen, TS & Møller, N 2015, 'Intact Pituitary Function is Decisive for the Catabolic Response to TNF-α: Studies of Protein, Glucose and Fatty Acid Metabolism in Hypopituitary and Healthy Subjects', The Journal of clinical endocrinology and metabolism, vol. 100, no. 2, pp. 578-86. https://doi.org/10.1210/jc.2014-2489

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title = "Intact Pituitary Function is Decisive for the Catabolic Response to TNF-α: Studies of Protein, Glucose and Fatty Acid Metabolism in Hypopituitary and Healthy Subjects",

abstract = "Context: TNF-α generates inflammatory responses and insulin resistance, lipolysis, and protein breakdown. It is unclear whether these changes depend on intact hypothalamo-pituitary stress hormone responses to trigger the release of cortisol and growth hormone. Objective: To define differential effects of TNF-α on glucose, protein, and lipid metabolism in hypopituitary patients (without intact hypothalamo-pituitary axis) and healthy controls. Design: Randomized, placebo controlled, single-blinded. Setting, Participants, and Intervention: We studied eight hypopituitary (HP) patients and eight matched control subjects [control volunteers (CTR)] twice during 4-h basal and 2-h hyperinsulinemic clamp conditions with isotope dilution during infusion of saline or TNF-α(12 ng/kg/h) for 6 h. Main Outcome Measures: Phenylalanine, urea, palmitate, and glucose fluxes and fat biopsies in basal and clamp periods. Results: TNF-α infusion significantly increased cortisol and GH levels in CTR but not in HP. TNF-α increased phenylalanine fluxes in both groups, with the increase being significantly greater in CTR, and raised urea flux by 40 % in CTR without any alteration in HP. Endogenous glucose production (EGP) was elevated in CTR compared to HP after TNF-α administration, whereas insulin sensitivity remained similarly unaffected in both groups. TNF-α increased whole body palmitate fluxes and decreased palmitate specific activity in CTR, but not in HP without statistical difference between groups. We did not detect significant effects TNF-α on lipase expression or regulation in fat. Conclusions: TNF-α increased both urea and amino acid fluxes and EGP significantly more in CTR compared to HP, suggesting that increases in endogenous cortisol and GH release are significant components of the metabolic response to TNF-α.",

author = "Ermina Bach and M{\o}ller, {Andreas B} and J{\o}rgensen, {Jens O L} and Vendelbo, {Mikkel H} and Niels Jessen and Olesen, {Jonas F} and Pedersen, {Steen B} and Nielsen, {Thomas Svava} and Niels M{\o}ller",

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AU - Bach, Ermina

AU - Møller, Andreas B

AU - Jørgensen, Jens O L

AU - Vendelbo, Mikkel H

AU - Jessen, Niels

AU - Olesen, Jonas F

AU - Pedersen, Steen B

AU - Nielsen, Thomas Svava

AU - Møller, Niels

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N2 - Context: TNF-α generates inflammatory responses and insulin resistance, lipolysis, and protein breakdown. It is unclear whether these changes depend on intact hypothalamo-pituitary stress hormone responses to trigger the release of cortisol and growth hormone. Objective: To define differential effects of TNF-α on glucose, protein, and lipid metabolism in hypopituitary patients (without intact hypothalamo-pituitary axis) and healthy controls. Design: Randomized, placebo controlled, single-blinded. Setting, Participants, and Intervention: We studied eight hypopituitary (HP) patients and eight matched control subjects [control volunteers (CTR)] twice during 4-h basal and 2-h hyperinsulinemic clamp conditions with isotope dilution during infusion of saline or TNF-α(12 ng/kg/h) for 6 h. Main Outcome Measures: Phenylalanine, urea, palmitate, and glucose fluxes and fat biopsies in basal and clamp periods. Results: TNF-α infusion significantly increased cortisol and GH levels in CTR but not in HP. TNF-α increased phenylalanine fluxes in both groups, with the increase being significantly greater in CTR, and raised urea flux by 40 % in CTR without any alteration in HP. Endogenous glucose production (EGP) was elevated in CTR compared to HP after TNF-α administration, whereas insulin sensitivity remained similarly unaffected in both groups. TNF-α increased whole body palmitate fluxes and decreased palmitate specific activity in CTR, but not in HP without statistical difference between groups. We did not detect significant effects TNF-α on lipase expression or regulation in fat. Conclusions: TNF-α increased both urea and amino acid fluxes and EGP significantly more in CTR compared to HP, suggesting that increases in endogenous cortisol and GH release are significant components of the metabolic response to TNF-α.

AB - Context: TNF-α generates inflammatory responses and insulin resistance, lipolysis, and protein breakdown. It is unclear whether these changes depend on intact hypothalamo-pituitary stress hormone responses to trigger the release of cortisol and growth hormone. Objective: To define differential effects of TNF-α on glucose, protein, and lipid metabolism in hypopituitary patients (without intact hypothalamo-pituitary axis) and healthy controls. Design: Randomized, placebo controlled, single-blinded. Setting, Participants, and Intervention: We studied eight hypopituitary (HP) patients and eight matched control subjects [control volunteers (CTR)] twice during 4-h basal and 2-h hyperinsulinemic clamp conditions with isotope dilution during infusion of saline or TNF-α(12 ng/kg/h) for 6 h. Main Outcome Measures: Phenylalanine, urea, palmitate, and glucose fluxes and fat biopsies in basal and clamp periods. Results: TNF-α infusion significantly increased cortisol and GH levels in CTR but not in HP. TNF-α increased phenylalanine fluxes in both groups, with the increase being significantly greater in CTR, and raised urea flux by 40 % in CTR without any alteration in HP. Endogenous glucose production (EGP) was elevated in CTR compared to HP after TNF-α administration, whereas insulin sensitivity remained similarly unaffected in both groups. TNF-α increased whole body palmitate fluxes and decreased palmitate specific activity in CTR, but not in HP without statistical difference between groups. We did not detect significant effects TNF-α on lipase expression or regulation in fat. Conclusions: TNF-α increased both urea and amino acid fluxes and EGP significantly more in CTR compared to HP, suggesting that increases in endogenous cortisol and GH release are significant components of the metabolic response to TNF-α.

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JO - The Journal of clinical endocrinology and metabolism

JF - The Journal of clinical endocrinology and metabolism

IS - 2

ER -

Intact Pituitary Function is Decisive for the Catabolic Response to TNF-α: Studies of Protein, Glucose and Fatty Acid Metabolism in Hypopituitary and Healthy Subjects

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