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Physiological roles of the GIP receptor in murine brown adipose tissue.

Publication ,  Journal Article
Beaudry, JL; Kaur, KD; Varin, EM; Baggio, LL; Cao, X; Mulvihill, EE; Bates, HE; Campbell, JE; Drucker, DJ
Published in: Mol Metab
October 2019

OBJECTIVE: Glucose-dependent insulinotropic polypeptide (GIP) is secreted from the gut in response to nutrient ingestion and promotes meal-dependent insulin secretion and lipid metabolism. Loss or attenuation of GIP receptor (GIPR) action leads to resistance to diet-induced obesity through incompletely understood mechanisms. The GIPR is expressed in white adipose tissue; however, its putative role in brown adipose tissue (BAT) has not been explored. METHODS: We investigated the role of the GIPR in BAT cells in vitro and in BAT-specific (GiprBAT-/-) knockout mice with selective elimination of the Gipr within the Myf5+ expression domain. We analyzed body weight, adiposity, glucose homeostasis, insulin and lipid tolerance, energy expenditure, food intake, body temperature, and iBAT oxygen consumption ex vivo. High-fat diet (HFD)-fed GiprBAT-/- mice were studied at room temperature (21 °C), 4 °C, and 30 °C ambient temperatures. RESULTS: The mouse Gipr gene is expressed in BAT, and GIP directly increased Il6 mRNA and IL-6 secretion in BAT cells. Additionally, levels of thermogenic, lipid and inflammation mRNA transcripts were altered in BAT cells transfected with Gipr siRNA. Body weight gain, energy expenditure, and glucose and insulin tolerance were normal in HFD-fed GiprBAT-/- mice housed at room temperature. However, GiprBAT-/- mice exhibited higher body temperatures during an acute cold challenge and a lower respiratory exchange ratio and impaired lipid tolerance at 21 °C. In contrast, body weight was lower and iBAT oxygen consumption was higher in HFD-fed mice housed at 4 °C but not at 30 °C. CONCLUSIONS: The BAT GIPR is linked to the control of metabolic gene expression, fuel utilization, and oxygen consumption. However, the selective loss of the GIPR within BAT is insufficient to recapitulate the findings of decreased weight gain and resistance to obesity arising in experimental models with systemic disruption of GIP action.

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Published In

Mol Metab

DOI

EISSN

2212-8778

Publication Date

October 2019

Volume

28

Start / End Page

14 / 25

Location

Germany

Related Subject Headings

  • Receptors, Gastrointestinal Hormone
  • Mice, Knockout
  • Mice, Inbred C57BL
  • Mice
  • Male
  • Female
  • Cell Line
  • Animals
  • Adipose Tissue, Brown
  • 3101 Biochemistry and cell biology
 

Citation

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Chicago
ICMJE
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Beaudry, J. L., Kaur, K. D., Varin, E. M., Baggio, L. L., Cao, X., Mulvihill, E. E., … Drucker, D. J. (2019). Physiological roles of the GIP receptor in murine brown adipose tissue. Mol Metab, 28, 14–25. https://doi.org/10.1016/j.molmet.2019.08.006
Beaudry, Jacqueline L., Kiran D. Kaur, Elodie M. Varin, Laurie L. Baggio, Xiemin Cao, Erin E. Mulvihill, Holly E. Bates, Jonathan E. Campbell, and Daniel J. Drucker. “Physiological roles of the GIP receptor in murine brown adipose tissue.Mol Metab 28 (October 2019): 14–25. https://doi.org/10.1016/j.molmet.2019.08.006.
Beaudry JL, Kaur KD, Varin EM, Baggio LL, Cao X, Mulvihill EE, et al. Physiological roles of the GIP receptor in murine brown adipose tissue. Mol Metab. 2019 Oct;28:14–25.
Beaudry, Jacqueline L., et al. “Physiological roles of the GIP receptor in murine brown adipose tissue.Mol Metab, vol. 28, Oct. 2019, pp. 14–25. Pubmed, doi:10.1016/j.molmet.2019.08.006.
Beaudry JL, Kaur KD, Varin EM, Baggio LL, Cao X, Mulvihill EE, Bates HE, Campbell JE, Drucker DJ. Physiological roles of the GIP receptor in murine brown adipose tissue. Mol Metab. 2019 Oct;28:14–25.
Journal cover image

Published In

Mol Metab

DOI

EISSN

2212-8778

Publication Date

October 2019

Volume

28

Start / End Page

14 / 25

Location

Germany

Related Subject Headings

  • Receptors, Gastrointestinal Hormone
  • Mice, Knockout
  • Mice, Inbred C57BL
  • Mice
  • Male
  • Female
  • Cell Line
  • Animals
  • Adipose Tissue, Brown
  • 3101 Biochemistry and cell biology