GIP Affects Hepatic Fat and Brown Adipose Tissue Thermogenesis but Not White Adipose Tissue Transcriptome in Type 1 Diabetes

Autor: Sebastian Møller Nguyen Heimbürger, Bjørn Hoe, Chris Neumann Nielsen, Natasha Chidekel Bergman, Kirsa Skov-Jeppesen, Bolette Hartmann, Jens Juul Holst, Flemming Dela, Julie Overgaard, Joachim Størling, Tina Vilsbøll, Thomas Fremming Dejgaard, Jesper Foged Havelund, Vladimir Gorshkov, Frank Kjeldsen, Nils Joakim Færgeman, Martin Rønn Madsen, Mikkel B Christensen, Filip Krag Knop
Rok vydání: 2022
Předmět:
Zdroj: The Journal of Clinical Endocrinology & Metabolism. 107:3261-3274
ISSN: 1945-7197
0021-972X
DOI: 10.1210/clinem/dgac542
Popis: Context Glucose-dependent insulinotropic polypeptide (GIP) has been proposed to exert insulin-independent effects on lipid and bone metabolism. Objective We investigated the effects of a 6-day subcutaneous 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 subcutaneous 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; glycated hemoglobin A1c 51 ± 10 mmol/mol [6.8 ± 3.1%]) experienced transiently increased circulating concentrations of nonesterified fatty acid (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 with placebo. After 6 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 with placebo infusion. WAT transcriptomic profile as well as circulating lipid species, proteome, markers of inflammation, and bone homeostasis were unaffected. Conclusion Six days of subcutaneous 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.
Databáze: OpenAIRE
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