Nicotinic Acid Increases Adiponectin Secretion from Differentiated Bovine Preadipocytes through G-Protein Coupled Receptor Signaling

Abstract

The transition period in dairy cows (3 weeks prepartum until 3 weeks postpartum) is associated with substantial mobilization of energy stores, which is often associated with metabolic diseases. Nicotinic acid (NA) is an antilipolytic and lipid-lowering compound used to treat dyslipidaemia in humans, and it also reduces non-esterified fatty acids in cattle. In mice the G-protein coupled receptor 109A (GPR109A) ligand NA positively affects the secretion of adiponectin, an important modulator of glucose and fat metabolism. In cattle, the corresponding data linking NA to adiponectin are missing. Our objective was to examine the effects of NA on adiponectin and AMPK protein abundance and the expression of mRNAs of related genes such as chemerin, an adipokine that enhances adiponectin secretion in vitro. Differentiated bovine adipocytes were incubated with pertussis toxin (PTX) to verify the involvement of GPR signaling, and treated with 10 or 15 µM NA for 12 or 24 h. NA increased adiponectin concentrations (p ≤ 0.001) and the mRNA abundances of GPR109A (p ≤ 0.05) and chemerin (p ≤ 0.01). Pre-incubation with PTX reduced the adiponectin response to NA (p ≤ 0.001). The NA-stimulated secretion of adiponectin and the mRNA expression of chemerin in the bovine adipocytes were suggestive of GPR signaling-dependent improved insulin sensitivity and/or adipocyte metabolism in dairy cows.

Expression of metabolic sensing receptors in adipose tissues of periparturient dairy cows with differing extent of negative energy balance

“…Thus we assume that HCAR2 is regulated through PPARG rather than by its endogenous ligand BHBA. Friedrichs, Sauerwein, Huber, Locher, Rehage, Meyer, Dänicke, Kuhla and Mielenz This assumption is in line with the study of Kopp et al (2014) in which the mRNA abundance of HCAR2 was not downregulated in bovine adipocytes in vitro by uncoupling of G-protein signalling using pertussis toxin.…”

“…Due to its function as metabolic sensor suppressing lipolysis during starvation, HCAR2 is an important target for a group of antilipolytic drugs (Offermanns et al, 2011). We recently reported that the HCAR2 ligand niacin stimulates the expression of HCAR2 in differentiated bovine preadipocytes in vitro (Kopp et al, 2014). Comparable to other mammalian species, the retroperitoneal AT (RPAT) from dairy cattle seems to have a higher lipolytic activity than subcutaneous AT (SCAT) due to the higher expression of hormone-sensitive lipase and the greater lipolytic response to adrenergic stimulation in RPAT (Locher et al, 2011;Kenéz et al, 2013).…”

Bta‐miR‐149‐5p inhibits proliferation and differentiation of bovine adipocytes through targeting CRTCs at both transcriptional and posttranscriptional levels

“…Forty hours posttransfection, the cells were induced to differentiation, with the first differentiation media supplemented with 0.5 mM hydrocortisol, IBMX (3.isobutyl‐1‐methylxanthine), dexamthasone 1 μM, and insulin 167 nM as described previously (Kopp et al, 2014). After 2 days, the cells were induced to differentiation with second differentiation medium containing DMEM‐F/12 medium with 10% fetal bovine serum and insulin 167 nM.…”

“…Forty hours posttransfection, the cells were induced to differentiation, with the first differentiation media supplemented with 0.5 mM hydrocortisol, IBMX (3.isobutyl-1-methylxanthine), dexamthasone 1 μM, and insulin 167 nM as described previously (Kopp et al, 2014).…”

Targeting molecules to medicine with mTOR, autophagy and neurodegenerative disorders

“…WISP1 fosters nuclear trafficking and activity of SIRT1 that results in neuronal protection and blocks apoptotic injury . WISP1 also regulates the post‐translational phosphorylation of AMPK . WISP1 modulates AMPK activation by differentially decreasing phosphorylation of TSC2 at serine 1387 , a target of AMPK, and increasing phosphorylation of TSC2 at threone 1462 , a target of Akt .…”