GIP affects hepatic fat and brown adipose tissue thermogenesis, but not white adipose tissue transcriptome in T1D
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GIP affects hepatic fat and brown adipose tissue thermogenesis, but not white adipose tissue transcriptome in T1D. / Heimbürger, Sebastian Møller Nguyen; Hoe, Bjørn; Nielsen, Chris Neumann; Bergman, Natasha Chidekel; Skov-Jeppesen, Kirsa; Hartmann, Bolette; Holst, Jens Juul; Dela, Flemming; Overgaard, Julie; Størling, Joachim; Vilsbøll, Tina; Dejgaard, Thomas Fremming; Havelund, Jesper Foged; Gorshkov, Vladimir; Kjeldsen, Frank; Færgeman, Nils Joakim Kaas; Madsen, Martin Rønn; Christensen, Mikkel B; Knop, Filip Krag.
In: Journal of Clinical Endocrinology and Metabolism, Vol. 107, No. 12, 2022, p. 3261–3274.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - GIP affects hepatic fat and brown adipose tissue thermogenesis, but not white adipose tissue transcriptome in T1D
AU - Heimbürger, Sebastian Møller Nguyen
AU - Hoe, Bjørn
AU - Nielsen, Chris Neumann
AU - Bergman, Natasha Chidekel
AU - Skov-Jeppesen, Kirsa
AU - Hartmann, Bolette
AU - Holst, Jens Juul
AU - Dela, Flemming
AU - Overgaard, Julie
AU - Størling, Joachim
AU - Vilsbøll, Tina
AU - Dejgaard, Thomas Fremming
AU - Havelund, Jesper Foged
AU - Gorshkov, Vladimir
AU - Kjeldsen, Frank
AU - Færgeman, Nils Joakim Kaas
AU - Madsen, Martin Rønn
AU - Christensen, Mikkel B
AU - Knop, Filip Krag
N1 - © The Author(s) 2022. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
PY - 2022
Y1 - 2022
N2 - AIMS/HYPOTHESIS: Glucose-dependent insulinotropic polypeptide (GIP) has been proposed to exert insulin-independent effects on lipid and bone metabolism. We investigated the effect of a 6-day s.c. GIP infusion on circulating lipids, white adipose tissue (WAT), brown adipose tissue (BAT), hepatic fat content, inflammatory markers, respiratory exchange ratio (RER), and bone homeostasis in patients with type 1 diabetes.METHODS: In a randomized, placebo-controlled, double-blind, crossover study, 20 men with type 1 diabetes underwent a 6-day continuous s.c. infusion with GIP (6 pmol/kg/min) and placebo (saline), with an interposed 7-day washout period.RESULTS: During GIP infusion, participants (26 ± 8 years [mean ± SD]; BMI 23.8 ± 1.8 kg/m2; HbA1c 51 ± 10 mmol/mol [6.8 ± 3.1%]) experienced transiently increased circulating concentrations of NEFA (p = 0.0005), decreased RER (p = 0.009), indication of increased fatty acid β-oxidation, and decreased levels of the bone resorption marker C-terminal telopeptide (p = 0.000072) compared to placebo. After six days of GIP infusion, hepatic fat content was increased by 12.6% (p = 0.007) and supraclavicular skin temperature, a surrogate indicator of BAT activity, was increased by 0.29°C (p < 0.000001) compared to placebo. WAT transcriptomic profile as well as circulating lipid species, proteome, markers of inflammation, and bone homeostasis were unaffected.CONCLUSIONS/INTERPRETATION: Six days s.c. GIP infusion in men with type 1 diabetes transiently decreased bone resorption and increased NEFA and β-oxidation. Further, hepatic fat content, and supraclavicular skin temperature were increased without affecting WAT transcriptomics, the circulating proteome, lipids, or inflammatory markers.
AB - AIMS/HYPOTHESIS: Glucose-dependent insulinotropic polypeptide (GIP) has been proposed to exert insulin-independent effects on lipid and bone metabolism. We investigated the effect of a 6-day s.c. GIP infusion on circulating lipids, white adipose tissue (WAT), brown adipose tissue (BAT), hepatic fat content, inflammatory markers, respiratory exchange ratio (RER), and bone homeostasis in patients with type 1 diabetes.METHODS: In a randomized, placebo-controlled, double-blind, crossover study, 20 men with type 1 diabetes underwent a 6-day continuous s.c. infusion with GIP (6 pmol/kg/min) and placebo (saline), with an interposed 7-day washout period.RESULTS: During GIP infusion, participants (26 ± 8 years [mean ± SD]; BMI 23.8 ± 1.8 kg/m2; HbA1c 51 ± 10 mmol/mol [6.8 ± 3.1%]) experienced transiently increased circulating concentrations of NEFA (p = 0.0005), decreased RER (p = 0.009), indication of increased fatty acid β-oxidation, and decreased levels of the bone resorption marker C-terminal telopeptide (p = 0.000072) compared to placebo. After six days of GIP infusion, hepatic fat content was increased by 12.6% (p = 0.007) and supraclavicular skin temperature, a surrogate indicator of BAT activity, was increased by 0.29°C (p < 0.000001) compared to placebo. WAT transcriptomic profile as well as circulating lipid species, proteome, markers of inflammation, and bone homeostasis were unaffected.CONCLUSIONS/INTERPRETATION: Six days s.c. GIP infusion in men with type 1 diabetes transiently decreased bone resorption and increased NEFA and β-oxidation. Further, hepatic fat content, and supraclavicular skin temperature were increased without affecting WAT transcriptomics, the circulating proteome, lipids, or inflammatory markers.
U2 - 10.1210/clinem/dgac542
DO - 10.1210/clinem/dgac542
M3 - Journal article
C2 - 36111559
VL - 107
SP - 3261
EP - 3274
JO - Journal of Clinical Endocrinology and Metabolism
JF - Journal of Clinical Endocrinology and Metabolism
SN - 0021-972X
IS - 12
ER -
ID: 321555611