Endocrinol Metab.  2021 Oct;36(5):997-1006. 10.3803/EnM.2021.1167.

Role of TRPV4 Channel in Human White Adipocytes Metabolic Activity

• Sánchez JC
• Valencia-Vásquez A
• García AM

• KMID: 2521948
• DOI: http://doi.org/10.3803/EnM.2021.1167

Abstract

Background
Intracellular calcium (Ca²⁺) homeostasis plays an essential role in adipocyte metabolism and its alteration is associated with obesity and related disorders. Transient receptor potential vanilloid 4 (TRPV4) channels are an important Ca²⁺ pathway in adipocytes and their activity is regulated by metabolic mediators such as insulin. In this study, we evaluated the role of TRPV4 channels in metabolic activity and adipokine secretion in human white adipocytes.
Methods
Human white adipocytes were freshly cultured and the effects of the activation and inhibition of TRPV4 channels on lipolysis, glucose uptake, lactate production, and leptin and adiponectin secretion were evaluated.
Results
Under basal and isoproterenol-stimulated conditions, TRPV4 activation by GSK1016709A decreased lipolysis whereas HC067047, an antagonist, increased lipolysis. The activation of TRPV4 resulted in increased glucose uptake and lactate production under both basal conditions and insulin-stimulated conditions; in contrast HC067047 decreased both parameters. Leptin production was increased, and adiponectin production was diminished by TRPV4 activation and its inhibition had the opposite effect.
Conclusion
Our results suggested that TRPV4 channels are metabolic mediators involved in proadipogenic processes and glucose metabolism in adipocyte biology. TRPV4 channels could be a potential pharmacological target to treat metabolic disorders.

Keyword

Adipocytes; TRPV4 protein; human; Metabolism; Lactates; Glucose

Figure

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  Fig. 1 Effect of transient receptor potential vanilloid 4 (TRPV4) effect on lipolysis. (A) Panel shows the effects of TRPV4 activation and inhibition on the glycerol production rate under basal conditions. (B) Panel shows the effect of TRPV4 on the glycerol production rate in isoproterenol (IPT)-stimulated conditions. The production rate was normalized to protein content. The data are expressed as median and interquartile range. All P values are shown as an exact Mann-Whitney U test value between TRPV4 activation and inhibition versus the basal and IPT-stimulated lipolysis rate (n=9 in all cases). GSK, GSK1016709A; HC, HC067047.

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  Fig. 2 Effect of transient receptor potential vanilloid 4 (TRPV4) on glucose uptake. (A) Panel shows the effects of TRPV4 activation and inhibition on glucose uptake under basal conditions. (B) Panel shows the effect of TRPV4 on glucose uptake under stimulation with insulin. The glucose uptake was normalized to protein content. The data are expressed as median and interquartile range. All P values are shown as an exact Mann-Whitney U test value between TRPV4 activation and inhibition versus basal and insulin-stimulated glucose uptake (n=9 in all cases). GSK, GSK1016709A; HC, HC067047; Ins, insulin.

• 

  Fig. 3 Transient receptor potential vanilloid 4 (TRPV4) effect on lactate production. (A) Panel shows the effect of TRPV4 activation and inhibition on lactate secretion in basal conditions. (B) Panel shows the effect of TRPV4 on lactate secretion under stimulation with insulin. The lactate secretion was normalized to protein content. The data are expressed in median and interquartile range. All P values are shown as an exact Mann-Whitney U test value between TRPV4 activation and inhibition versus the basal and insulin-stimulated lactate production (n=9 in all cases). GSK, GSK1016709A; HC, HC067047.

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  Fig. 4 The effect of transient receptor potential vanilloid 4 (TRPV4) on the linear relationship between glucose uptake and lactate production in all the experimental conditions, as indicated. The individual values are presented as separate points (n=9 in all cases). Ins, insulin; GSK, GSK1016709A; HC, HC067047. aDenotes significance.

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  Fig. 5 Effect of transient receptor potential vanilloid 4 (TRPV4) and insulin on hormone production. (A) Panel shows the effects of TRPV4 activation and inhibition on leptin production under basal conditions. (B) Panel shows the effect of TRPV4 on adiponectin production. Hormone production was normalized to protein content. The data are expressed as median and interquartile range. All P values are shown as an exact Mann-Whitney U test between TRPV4 activation and inhibition versus basal hormone production (n=9 in all cases). GSK, GSK1016709A; HC, HC067047.

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