Faculty of Health Sciences, Technological University of Pereira, La Julita, Pereira, Colombia.
Endocrinol Metab (Seoul). 2021 Oct;36(5):997-1006. doi: 10.3803/EnM.2021.1167. Epub 2021 Oct 14.
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.
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.
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.
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.
细胞内钙（Ca2+）稳态在脂肪细胞代谢中起着至关重要的作用，其改变与肥胖和相关疾病有关。瞬时受体电位香草醛 4（TRPV4）通道是脂肪细胞中重要的 Ca2+途径，其活性受代谢调节剂如胰岛素的调节。在这项研究中，我们评估了 TRPV4 通道在人类白色脂肪细胞代谢活性和 adipokine 分泌中的作用。
新鲜培养人白色脂肪细胞，并评估 TRPV4 通道的激活和抑制对脂肪分解、葡萄糖摄取、乳酸生成以及瘦素和脂联素分泌的影响。
在基础和异丙肾上腺素刺激条件下，GSK1016709A 激活 TRPV4 可减少脂肪分解，而拮抗剂 HC067047 则增加脂肪分解。TRPV4 的激活导致基础条件和胰岛素刺激条件下葡萄糖摄取和乳酸生成增加；相反，HC067047 降低了这两个参数。TRPV4 的激活增加了瘦素的产生，减少了脂联素的产生，而其抑制则产生相反的效果。
我们的结果表明，TRPV4 通道是参与脂肪生成过程和葡萄糖代谢的代谢调节剂。TRPV4 通道可能是治疗代谢紊乱的潜在药物靶点。
