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J Nutr Biochem. 2015 May;26(5):541-8. doi: 10.1016/j.jnutbio.2014.12.011. Epub 2015 Feb 12.

Palmitic acid induces central leptin resistance and impairs hepatic glucose and lipid metabolism in male mice.

Author information

1
School of Medicine, University of Wollongong and Illawarra Health and Medical Research Institute, NSW 2522, Australia.
2
School of Medicine, University of Wollongong and Illawarra Health and Medical Research Institute, NSW 2522, Australia; Schizophrenia Research Institute (SRI), 405 Liverpool St, Sydney, NSW 2010, Australia.
3
School of Medicine, University of Wollongong and Illawarra Health and Medical Research Institute, NSW 2522, Australia; ANSTO Life Sciences, Australian Nuclear Science and Technology Organisation (ANSTO), Lucas Heights, NSW 2234, Australia.
4
School of Medicine, University of Wollongong and Illawarra Health and Medical Research Institute, NSW 2522, Australia; Schizophrenia Research Institute (SRI), 405 Liverpool St, Sydney, NSW 2010, Australia. Electronic address: xhuang@uow.edu.au.

Abstract

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 (icv) 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/6J male mice. We found that the icv 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-FOXO1) and a pro-inflammatory response (TNF-α, IL1-β, IL-6 and pIκBa) in the mediobasal hypothalamus and paraventricular hypothalamic nuclei. Furthermore, the pre-administration of icv 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.

KEYWORDS:

Glucose metabolism; Hypothalamus; Inflammation; Leptin resistance; Lipid metabolism; Palmitic acid

PMID:
25724108
DOI:
10.1016/j.jnutbio.2014.12.011
[Indexed for MEDLINE]

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