Nesfatin-1 Stimulates Fatty-Acid Oxidation by Activating AMP-Activated Protein Kinase in STZ-Induced Type 2 Diabetic Mice

Abstract

Nesfatin-1 is an anorexigenic peptide involved in energy homeostasis. Recently, nesfatin-1 was reported to decrease blood glucose level and improve insulin sensitivity in high-fat diet-fed rats. However, little information is known about the influence of nesfatin-1 on lipid metabolism either in physiological or diabetic condition. This study undertook whether nesfatin-1 was involved in the pathophysiology in Streptozotocin-induced type 2 diabetic mice (T2DM), which was induced by a combination of high-calorie diet and two low-doses Streptozotocin. We observed that plasma nesfatin-1 was significantly increased while expression of nesfatin-1 neurons were decreased in hypothalamus in diabetes group compared to only high-calorie diet control group; intravenous injection of nesfatin-1 decreased 0–1h, 0–2h, 0–3h cumulative food intake in T2DM, but 0–24h total food intake had no difference between groups. Body weight and plasma FFA were normalized after nesfatin-1(10 µg/Kg) administration for 6 days. These results suggested that nesfatin-1 improved lipid disorder in T2DM. It was found that blood glucose and insulin resistance coefficient decreased with treatment of nesfatin-1 (both in 1 µg/Kg and 10 µg/Kg doses) in diabetes mice. For further understanding the role of nesfatin-1 on lipid metabolism, we detected p-AMPK and p-ACC of skeletal muscle in T2DM using western blotting. The expression of p-AMPK and p-ACC increased when nesfatin-1 was given with doses 1 µg/Kg but not in doses 10 µg/Kg. Taken together, nesfatin-1 participated in the development of T2DM and stimulated free fatty acid utilization via AMPK-ACC pathway in skeletal muscle in T2DM.

Nesfatin-1 promotes brown adipocyte phenotype

“…This finding extends the action of nesfatin-1 to brown adipocytes and provides further evidence supporting its critical role in the regulation of lipid homeostasis. Consistent with this observation, previous studies have demonstrated that nesfatin-1 inhibits lipid accumulation in 3T3-L1 cells16 and hepatocytes17, as well as reduces circulating fatty acid levels in diet-induced obese mice1718. NUCB2/nesfatin-1 is expressed abundantly in the X/A like cells of gastric mucosa and may be released into the circulation to exert actions in both central and peripheral tissues.…”

A novel function of NUCB2 in promoting the development and invasion of renal cell carcinoma

“…Recently, overexpression of NUCB2 in clear cell RCC was observed to contribute to malignant clinical pathology and a poor prognosis in renal cancer, indicating that it may be a novel biomarker (16). Based on a previous publication by the present authors (10), in the present study NUCB2 expression in ACHN, 786-O, PC-3 and DU 145 cells was verified, and a significant high expression was demonstrated in renal carcinoma 786-O cells. Therefore, the NUCB2 gene was knocked down in the 786-O cells in order to study its function.…”

“…As previously described, it has been report that the fasting plasma NUCB2 levels were significantly decreased in patients with type 2 diabetes compared with healthy or type 1 diabetes subjects (9). Additionally, plasma NUCB2 appears to regulate glucose and fatty acid metabolism (10,11). NUCB2 also inhibits the apoptosis of pancreatic cells, which tends to accelerate the development of metabolic disorders (12).…”

Relation of serum and vitreous nesfatin-1 concentrations with diabetic retinopathy

“…Treatment with nesfatin-1 decreased both blood glucose and insulin resistance in diabetic mice 11. Nesfatin-1 infusion into the third cerebral ventricle improved insulin sensitivity in mice with diet-induced insulin resistance 12.…”