Version 1
: Received: 26 August 2020 / Approved: 27 August 2020 / Online: 27 August 2020 (10:32:16 CEST)
How to cite:
Geisler, C.; Renquist, B. The Role of GPR109a Signaling in Niacin Induced Effects on Fed and Fasted Hepatic Metabolism. Preprints2020, 2020080610. https://doi.org/10.20944/preprints202008.0610.v1
Geisler, C.; Renquist, B. The Role of GPR109a Signaling in Niacin Induced Effects on Fed and Fasted Hepatic Metabolism. Preprints 2020, 2020080610. https://doi.org/10.20944/preprints202008.0610.v1
Geisler, C.; Renquist, B. The Role of GPR109a Signaling in Niacin Induced Effects on Fed and Fasted Hepatic Metabolism. Preprints2020, 2020080610. https://doi.org/10.20944/preprints202008.0610.v1
APA Style
Geisler, C., & Renquist, B. (2020). The Role of GPR109a Signaling in Niacin Induced Effects on Fed and Fasted Hepatic Metabolism. Preprints. https://doi.org/10.20944/preprints202008.0610.v1
Chicago/Turabian Style
Geisler, C. and Benjamin Renquist. 2020 "The Role of GPR109a Signaling in Niacin Induced Effects on Fed and Fasted Hepatic Metabolism" Preprints. https://doi.org/10.20944/preprints202008.0610.v1
Abstract
Signaling through GPR109a, the putative receptor for the endogenous ligand β-OH butyrate, inhibits adipose tissue lipolysis. Niacin, an anti-atherosclerotic drug that can induce insulin resistance, activates GPR109a at nM concentrations. GPR109a is not essential for niacin to improve serum lipid profiles. To better understand the involvement of GPR109a signaling in regulating glucose and lipid metabolism, we treated GPR109a wildtype (+/+) and knockout (-/-) mice with repeated overnight injections of saline or niacin in physiological states characterized by low (ad libitum fed) or high (16h fasted) concentrations of the endogenous ligand, β-OH butyrate. In the fed state, niacin increased expression of PEPCK mRNA independent of genotype, while increasing CPT1 mRNA only in GPR109a -/- mice. Niacin decreased fasting serum non-esterified fatty acid concentrations in both GPR109a +/+ and -/- mice. Independent of GPR109a expression, niacin blunted fast-induced hepatic triglyceride accumulation and peroxisome proliferator activated receptor α (PPARα) mRNA expression. Surprisingly, GPR109a knockout did not affect glucose or lipid homeostasis or hepatic gene expression in either fed or fasted mice. In turn, GPR109a does not appear to be essential for the metabolic response to the ketogenic state or the pharmacological benefits associated with niacin.
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
