Central nesfatin‐1 activates lipid mobilization in adipose tissue and fatty acid oxidation in muscle via the sympathetic nervous system. (3rd January 2020)

• Record Type: Journal Article
• Authors: Liu, Yuan; Chen, Xi; Qu, Yan; Song, Limin; Lin, Qian; Li, Manwen; Su, Kaizhen; Li, Yanrun; Dong, Jing
• Is Part Of: BioFactors. Volume 46:Number 3(2020)
• Page Start: 454
• Page End: 464
• Publication Date: 2020-01-03
• Subjects: hypothalamic nucleus -- lipid metabolism -- nesfatin‐1 -- sympathetic nervous system -- type 2 diabetes mellitus; Vitamins -- Physiological effect -- Periodicals; Trace elements -- Physiological effect -- Periodicals; Growth factors -- Physiological effect -- Periodicals; Plant growth promoting substances -- Physiological effect -- Periodicals; Biochemistry -- Periodicals; Nutritional Physiological Phenomena -- Periodicals; Trace Elements -- metabolism -- Periodicals; Vitamins -- metabolism -- Periodicals; Molecular Biology -- Periodicals; 612.399
• DOI: 10.1002/biof.1600
• Languages: English
• ISSNs: 0951-6433

Abstract

Abstract: Little is known about the influence of central nesfatin‐1 on lipid metabolism under diabetic conditions. The main objective of this study was to characterize the mechanisms by which central nesfatin‐1 regulates lipid metabolism in streptozotocin (STZ)‐induced type 2 diabetes mellitus (T2DM) and whether the sympathetic nervous system is involved. Male Kunming mice were fed high‐fat diets (HFDs) and were treated twice with low‐dose STZ (100 mg/kg, intraperitoneal [IP]) to generate the T2DM model. Pharmacological adrenergic blockage (phentolamine 10 mg/kg, propranolol 0.017 mmol) and surgical denervation of sympathetic nervous system of the hindlimb and inguinal fat were used to block nerve conduction to determine whether the effect of central nesfatin‐1 required the hypothalamic‐sympathetic nervous system axis. Plasma free fatty acid (FFA) and insulin levels were measured. AMP‐activated protein kinase (AMPK) levels in skeletal muscle and hormone‐sensitive lipase and adipose triglycerides lipase (HSL/ATGL) levels in white adipose tissue (WAT) were measured using western blot. mRNA expression of AMPK was measured. We found that there were significantly fewer NUCB2/nesfatin‐1 immunoreactive neurons in the paraventricular nucleus (PVN) and supraoptic nucleus (SON) in T2DM mice. Central nesfatin‐1 administration decreased levels of plasma FFA significantly and activated AMPK to enhance fatty‐acid oxidation in skeletal muscle in T2DM mice. In addition, HSL and ATGL were significantly activated during triglyceride mobilization in WAT triggered by central nesfatin‐1 administration. Adrenergic blockade and morphological denervation of the sciatic and femoral nerves reduced these changes. Taken together, these data suggest that central nesfatin‐1 regulates peripheral lipid metabolism in type 2 diabetes via the sympathetic nervous system.