Journal
JOURNAL OF NUTRITIONAL BIOCHEMISTRY
Volume 26, Issue 5, Pages 541-548Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.jnutbio.2014.12.011
Keywords
Palmitic acid; Leptin resistance; Hypothalamus; Inflammation; Glucose metabolism; Lipid metabolism
Funding
- Diabetes Australia Research Trust Research Projects
- National Health and Medical Research Council of Australia [NHMRC 573441]
- Schizophrenia Research Institute
Ask authors/readers for more resources
The consumption of diets rich in saturated fat largely contributes to the development of obesity in modern societies. A diet high in saturated fats can induce inflammation and impair leptin signaling in the hypothalamus. However, the role of saturated fatty acids on hypothalamic leptin signaling, and hepatic glucose and lipid metabolism remains largely undiscovered. In this study, we investigated the effects of intracerebroventricular (icy) administration of a saturated fatty acid, palmitic acid (PA, C16:0), on central leptin sensitivity, hypothalamic leptin signaling, inflammatory molecules and hepatic energy metabolism in C57BL/6 J male mice. We found that the icy administration of PA led to central leptin resistance, evidenced by the inhibition of central leptin's suppression of food intake. Central leptin resistance was concomitant with impaired hypothalamic leptin signaling (JAK2-STAT3, PKB/Akt-FOX01) and a pro-inflammatory response (TNF-alpha, HA-beta, IL-6 and pIkBa) in the mediobasal hypothalamus and paraventricular hypothalamic nuclei. Furthermore, the pre-administration of icy PA blunted the effect of leptin-induced decreases in mRNA expression related to gluconeogenesis (G6Pase and PEPCK), glucose transportation (GLUT2) and lipogenesis (FAS and SCD1) in the liver of mice. Therefore, elevated central PA concentrations can induce pro-inflammatory,responses and leptin resistance, which are associated with disorders of energy homeostasis in the liver as a result of diet-induced obesity. (C) 2015 Elsevier Inc. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available