Abstract
We recently identified a novel small secretory protein, neurosecretory protein GL (NPGL), in the vertebrate hypothalamus. We revealed that NPGL is involved in energy homeostasis using intracerebroventricular infusion in rodents. However, the effect of NPGL through peripheral administration remains to be elucidated and may be important for therapeutic use. In this study, we performed subcutaneous infusion of NPGL in mice for 12 days and found that it accelerated fat accumulation in white adipose tissue (WAT) without increasing in body mass gain and food intake. The mass of the testis, liver, kidney, heart, and gastrocnemius muscle remained unchanged. Analysis of mRNA expression by quantitative reverse transcription-polymerase chain reaction showed that proopiomelanocortin was suppressed in the hypothalamus by the infusion of NPGL. We observed a decreasing tendency in serum triglyceride levels due to NPGL, while serum glucose, insulin, leptin, and free fatty acids levels were unchanged. These results suggest that the peripheral administration of NPGL induces fat accumulation in WAT via the hypothalamus.
Highlights
The World Health Organization (WHO) reported that 400 million people are obese, and over 1.6 billion adults are overweight worldwide [1]
neurosecretory protein GL (NPGL) slightly increased body mass gain and cumulative food intake without significant differences (Figure 1A and B), it significantly increased the mass of inguinal white adipose tissue (WAT) and perirenal WAT (Figure 2A)
We demonstrated that subcutaneous infusion of NPGL stimulated fat accumulation in WAT, corresponding to our previous study showing that i.c.v. infusion of NPGL enlarged adipocytes in WAT [17, 19]
Summary
The World Health Organization (WHO) reported that 400 million people are obese, and over 1.6 billion adults are overweight worldwide [1]. Obesity is caused by fat accumulation due to excess calorie intake or inadequate energy consumption and has been shown to increase the risk of developing various diseases, including diabetes, hypertension, and hyperlipidemia [2, 3, 4, 5, 6]. There is a strong focus on researching energy homeostasis, including in feeding behavior and lipid metabolism. A hormone secreted by the pancreas, suppresses feeding behavior, mediated by cocaine- and amphetamine-regulated transcript (CART) in the hypothalamus [11]. Orexigenic/anorexigenic factors and their signaling pathways regulate feeding behavior and lipid metabolism. The mechanism of lipid metabolism is not fully understood, and further research is required to regulate fat mass in various tissues
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