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Nicotinic acid increases adiponectin secretion from differentiated bovine preadipocytes through G-protein coupled receptor signaling.

Kopp C, Hosseini A, Singh SP, Regenhard P, Khalilvandi-Behroozyar H, Sauerwein H, Mielenz M - Int J Mol Sci (2014)

Bottom Line: 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.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).

View Article: PubMed Central - PubMed

Affiliation: Institute of Animal Science, Physiology & Hygiene Unit, University of Bonn, 53115 Bonn, Germany. christina.kopp@uni-bonn.de.

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.

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The effects of nicotinic acid (NA) on adiponectin concentrations (means ± SEM) in cell culture supernatants of differentiated bovine adipocytes (n = 5). After 4 h of serum starvation, the adipocytes were pre-incubated with pertussis toxin (PTX (+)) or without (PTX (−)) (100 ng/mL) for 16 h and then treated for 12 or 24 h with 10 or 15 µM NA or PBS (vehicle control). The different lower case letters designate significant differences (p ≤ 0.005) between the NA treatments and the controls for the PTX (−) cells; the different upper case letters designate significant differences (p ≤ 0.001) between the NA treatments and the controls for the PTX (+) cells. Significant differences (*** p ≤ 0.001) due to PTX (+) or PTX (−) pre-incubation for each NA treatment group are indicated with asterisks.
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ijms-15-21401-f001: The effects of nicotinic acid (NA) on adiponectin concentrations (means ± SEM) in cell culture supernatants of differentiated bovine adipocytes (n = 5). After 4 h of serum starvation, the adipocytes were pre-incubated with pertussis toxin (PTX (+)) or without (PTX (−)) (100 ng/mL) for 16 h and then treated for 12 or 24 h with 10 or 15 µM NA or PBS (vehicle control). The different lower case letters designate significant differences (p ≤ 0.005) between the NA treatments and the controls for the PTX (−) cells; the different upper case letters designate significant differences (p ≤ 0.001) between the NA treatments and the controls for the PTX (+) cells. Significant differences (*** p ≤ 0.001) due to PTX (+) or PTX (−) pre-incubation for each NA treatment group are indicated with asterisks.

Mentions: To test whether NA affects the secretion of adiponectin, the differentiated bovine adipocytes were stimulated with two different concentrations of NA (10 and 15 µM) for 12 or 24 h. Compared to the NA-free controls, the adiponectin concentrations in the cell culture supernatants were 4-fold increased following stimulation with 10 or 15 µM NA for 12 h (p ≤ 0.001) and approximately 5- and 6-fold increased following 24 h treatments with 10 and 15 µM NA, respectively (p ≤ 0.001) (Figure 1). To assess whether the effects of NA were mediated by GPR signaling, the experiments were performed following pre-incubation with PTX (100 ng/mL) for 16 h. For both NA doses and both durations of treatment, the pre-incubation with PTX decreased the adiponectin concentrations to values between 62 and 87 ng/mL; however, these concentrations were consistently higher than those observed in the relevant NA-free control (39 ng/mL; p ≤ 0.001). Comparisons of the PTX pre-incubation groups revealed that the adiponectin concentrations were approximately 3 times lower following PTX pre-incubation in the 10 µM NA group at both durations (p ≤ 0.001). The adiponectin concentrations in the supernatants from the PTX (+) group were reduced by 3- and 3.5-fold (p ≤ 0.001) following treatment with 15 µM NA regardless of time when compared with the corresponding PTX (−) group (Figure 1).


Nicotinic acid increases adiponectin secretion from differentiated bovine preadipocytes through G-protein coupled receptor signaling.

Kopp C, Hosseini A, Singh SP, Regenhard P, Khalilvandi-Behroozyar H, Sauerwein H, Mielenz M - Int J Mol Sci (2014)

The effects of nicotinic acid (NA) on adiponectin concentrations (means ± SEM) in cell culture supernatants of differentiated bovine adipocytes (n = 5). After 4 h of serum starvation, the adipocytes were pre-incubated with pertussis toxin (PTX (+)) or without (PTX (−)) (100 ng/mL) for 16 h and then treated for 12 or 24 h with 10 or 15 µM NA or PBS (vehicle control). The different lower case letters designate significant differences (p ≤ 0.005) between the NA treatments and the controls for the PTX (−) cells; the different upper case letters designate significant differences (p ≤ 0.001) between the NA treatments and the controls for the PTX (+) cells. Significant differences (*** p ≤ 0.001) due to PTX (+) or PTX (−) pre-incubation for each NA treatment group are indicated with asterisks.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4264232&req=5

ijms-15-21401-f001: The effects of nicotinic acid (NA) on adiponectin concentrations (means ± SEM) in cell culture supernatants of differentiated bovine adipocytes (n = 5). After 4 h of serum starvation, the adipocytes were pre-incubated with pertussis toxin (PTX (+)) or without (PTX (−)) (100 ng/mL) for 16 h and then treated for 12 or 24 h with 10 or 15 µM NA or PBS (vehicle control). The different lower case letters designate significant differences (p ≤ 0.005) between the NA treatments and the controls for the PTX (−) cells; the different upper case letters designate significant differences (p ≤ 0.001) between the NA treatments and the controls for the PTX (+) cells. Significant differences (*** p ≤ 0.001) due to PTX (+) or PTX (−) pre-incubation for each NA treatment group are indicated with asterisks.
Mentions: To test whether NA affects the secretion of adiponectin, the differentiated bovine adipocytes were stimulated with two different concentrations of NA (10 and 15 µM) for 12 or 24 h. Compared to the NA-free controls, the adiponectin concentrations in the cell culture supernatants were 4-fold increased following stimulation with 10 or 15 µM NA for 12 h (p ≤ 0.001) and approximately 5- and 6-fold increased following 24 h treatments with 10 and 15 µM NA, respectively (p ≤ 0.001) (Figure 1). To assess whether the effects of NA were mediated by GPR signaling, the experiments were performed following pre-incubation with PTX (100 ng/mL) for 16 h. For both NA doses and both durations of treatment, the pre-incubation with PTX decreased the adiponectin concentrations to values between 62 and 87 ng/mL; however, these concentrations were consistently higher than those observed in the relevant NA-free control (39 ng/mL; p ≤ 0.001). Comparisons of the PTX pre-incubation groups revealed that the adiponectin concentrations were approximately 3 times lower following PTX pre-incubation in the 10 µM NA group at both durations (p ≤ 0.001). The adiponectin concentrations in the supernatants from the PTX (+) group were reduced by 3- and 3.5-fold (p ≤ 0.001) following treatment with 15 µM NA regardless of time when compared with the corresponding PTX (−) group (Figure 1).

Bottom Line: 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.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).

View Article: PubMed Central - PubMed

Affiliation: Institute of Animal Science, Physiology & Hygiene Unit, University of Bonn, 53115 Bonn, Germany. christina.kopp@uni-bonn.de.

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.

Show MeSH
Related in: MedlinePlus