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A PDE1 inhibitor reduces adipogenesis in mice via regulation of lipolysis and adipogenic cell signaling

Nam-Jun Kim,J. Baek,Jinah Lee,Hye-Young Kim,Jun-Kyu Song,Kyung-Hee Chun

Published 2019 in Experimental and Molecular Medicine

ABSTRACT

Vinpocetine, a phosphodiesterase (PDE) type-1 inhibitor, increases cAMP and cGMP levels and is currently used for the management of cerebrovascular disorders, such as stroke, cerebral hemorrhage, and cognitive dysfunctions. In this study, we first determined that vinpocetine effectively suppressed adipogenesis and lipid accumulation. However, we questioned which molecular mechanism is involved because the role of PDE in adipogenesis is still controversial. Vinpocetine decreased adipogenic cell signaling, including the phosphorylation of ERK, AKT, JAK2, and STAT3, and adipokine secretion, including IL-6, IL-10, and IFN-α. Interestingly, vinpocetine increased the phosphorylation of HSL, suggesting the induction of the lipolysis pathway. Moreover, vinpocetine increased UCP1 expression via increasing cAMP and PKA phosphorylation. The administration of vinpocetine with a normal-chow diet (NFD) or a high-fat diet (HFD) in mice attenuated body weight gain in mice fed both the NFD and HFD. These effects were larger in the HFD-fed mice, without a difference in food intake. Vinpocetine drastically decreased fat weight and adipocyte cell sizes in gonadal and inguinal white adipose tissues and in the liver in both diet groups. Serum triacylglycerol levels and fasting blood glucose levels were reduced by vinpocetine treatment. This study suggested that vinpocetine prevents adipocyte differentiation through the inhibition of adipogenesis-associated cell signaling in the early stages of adipogenesis. Moreover, upregulating cAMP levels leads to an increase in lipolysis and UCP1 expression and then inhibits lipid accumulation. Therefore, we suggest that vinpocetine could be an effective agent for treating obesity, as well as improving cognition and cardiovascular function in older individuals. A compound extracted from the periwinkle plant can limit the over-production of fat cells and may be a useful agent for treating obesity. Being overweight is the result of changes in the size and number of fat cells, or adipocytes, in the body. Scientists are searching for molecules that can limit the growth and replication of adipocytes, but many anti-obesity agents found to date have unpleasant side-effects. Kyung-Hee Chun at Yonsei University in Seoul, South Korea and co-workers examined the effects of 502 naturally occuring compounds on adipocyte differentiation in cell culture. One compound called vincamine, which is safely used to treat vascular diseases in the brain, decreased cell signaling pathways involved in adipocyte generation in mice and also lowered fasting blood glucose levels.

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