Obesity is generally defined as an excess of body fats and related to weight gain. The hypothalamic arcuate nucleus (ARC) is responsible for regulating peripheral signals that control food intake and energy balance. Uncoupling protein-1 (UCP-1) and UCP-2 are related-genes that adjust body weight. The aim of this study is to explore the effect of fat-1 gene on body weight. We found that the weight/length ratios of fat-1 transgenic mice were smaller than wild-type (WT) mice. We hypothesized that an increase in the levels of n-3 PUFAs might alter the expression of hypothalamic neuropeptide and lead to weight loss in fat-1 mice because fat-1 gene transforms n-6 polyunsaturated fatty acids (PUFAs) to n-3 PUFAs. Therefore, the appetite-regulating neuropeptides in the hypothalamic ARC, including neuropeptide Y (NPY), agouti-related peptides (AgRP), proopiomelanocortin (POMC), cocaine and amphetamine regulated transcript (CART), and ghrelin, were measured by Immunofluorescence. The mRNA levels of UCP-1 in brown adipose tissues and UCP-2 in white adipose tissues were measured by RT-PCR. The protein levels of UCP-2 in white adipose tissues also were measured by Western Blot. Compared with WT mice, the levels of CART, POMC and ghrelin increased, the levels of NPY and AgRP decreased, whereas the mRNA levels of UCP-1, UCP-2 increased, the protein levels of UCP-2 increased in fat-1 mice. The results indicated that the fat-1 gene or n-3 PUFAs participate in inhibition of body weight by regulating the expressions of appetite neuropeptide and uncoupling protein.
Hypothalamus, fat-1 Gene, Neuropeptide, Body Weight
- Hayes M R. Scientific familial lessons in ingestive behavior research: 2016 Alan N.
- Epsteinresearch award. J. Physiology & behavior. 2017, 176:214-216. PMID: 28137426
- Gale S.M., V.D. Castracane, and C.S. Mantzoros, Energy homeostasis, obesity and eating disorders: recent advances in endocrinology. J. Nutr, 2004. 134(2): p. 295-8. PMID: 14747663
- Ferrario C R, Labouèbe G, Liu S, et al. Homeostasis Meets Motivation in the Battle to Control Food Intake. J. Journal of Neuroscience the Official Journal of the Society for Neuroscience. 2016, 36(45):11469-11481. PMID: 27911750
- Cone R D, Cowley M A, Butler A A, et al. The arcuate nucleus as a conduit for diverse signals relevant to energy homeostasis. J. International Journal of Obesity & Related Metabolic Disorders Journal of the International Association for the Study of Obesity. 2001, 25 Suppl 5(s182):S63-7. PMID: 11840218
- Klein M O, Mackay H, Edwards A, et al. POMC and NPY mRNA expression during development is increased in rat offspring brain from mothers fed with a high fat diet. J. International Journal of Developmental Neuroscience. 2017.03.004. 64:14-20. PMID: 28323039
- Gillard L, Billiauws L, Stan-Iuga B, et al. Enhanced Ghrelin Levels and Hypothalamic Orexigenic AgRP and NPY Neuropeptide Expression in Models of Jejuno-Colonic Short Bowel Syndrome. J. Scientific Reports. 2016, 6:28345.PMID: 27323884
- R. Pandit, J. W. de Jong, L. J. M. J. Vanderschuren. Neurobiology of overeating and obesity: the role of melanocortins and beyond. European journal of pharmacology. 660 (2011) 28-42. PMID: 21295024
- Park B G, Park Y S, Park J W, et al. Anti-obesity potential of enzymatic fragments of hyaluronan on high-fat diet-induced obesity in C57BL/6 mice. J. Biochemical & Biophysical Research Communications. 2016, 473(1): 290-295. PMID: 27012203
- Hill JO，Peters JC，LinD，et a1. Lipid accumulation and body fat distribution is influenced by type of dietary fat fed to rats. J. Int J Obes Relat Metab Disord. 1993, 17(4):223-226. PMID: 8387971
- Huangx F，XinX，McLennanP，et a1. Role of fat amount and type in ameliorating Diet inducedobesity：insights at the levelof hypothalamie arcuate nucleus leptin receptor, neuropeptide Y and proopiomelanocortin mRNA expression. J. Diabetes Obes Metab. 2004, 6(1):35-44. PMID: 14686961
- Ji S, Hardy R W, Wood P A. Transgenic Expression of n-3 Fatty Acid Desaturase (fat-1) in C57/BL6 Mice: Effects on Glucose Homeostasis and Body Weight. J. Journal of Cellular Biochemistry. 2009, 107(4):809. PMID: 19396841
- Jing X. Kang. Fat-1 Transgenic Mice: A New Model for Omega-3 Research. Prostaglandins Leukot Essent Fatty Acid. 2007; 77(5-6): 263–267. PMID: 18042365
- L.J. QIAO, Z. ZHENG, W.H. Ma. Effect of PUFA-containing diet on gut microbiota and fat metabolism-related genes in rats. Food Sci. 17 (2014) 231–235.
- D.E. Cintra, E.R. Ropelle, J.C. Moraes. Unsaturated fatty acids revert diet-induced hypothalamic inflammation in obesity. J. PLoS One. 7 (2012) e30571. PMID: 22279596
- P. J. White, P. L. Mitchell, M. Schwab. Transgenic ω-3 PUFA enrichment alters morphology and gene expression profile in adipose tissue of obese mice: Potential role for protectins. Metabolism. 64 (2015) 666-676. PMID: 25726444
- M. Goebel-Stengel, L. Wang. Central and peripheral expression and distribution of NUCB2/nesfatin-1. Curr. Pharm. Des. 19 (2013) 6935–6940. PMID: 23537079
- Y. Avraham, J. Katzhendler, L. Vorobeiv. Novel acylethanolamide derivatives that modulate body weight through enhancement of hypothalamic pro-opiomelanocortin (POMC) and/or decreased neuropeptide Y (NPY). J. Med. Chem. 56 (2013) 1811–1829.
- Shuangshuang Ma, Yinlin Ge, Xiaoying Gai, Meilan Xue, Ning Li, Jingxuan Kang, Jianbo Wan, Jinyu Zhang. Transgenic n-3 PUFAs enrichment leads to weight loss via modulating neuropeptides in hypothalamus. Neuroscience Letters, Volume 611. 12 January 2016, Pages 28-32, ISSN 0304-3940. PMID: 26610903
- Cabral A, Portiansky E, Sánchezjaramillo E, et al. Ghrelin activates hypophysiotropic corticotropin-releasing factor neurons independently of the arcuate nucleus. J. Psychoneuroendocrinology. 2016, 67:27-39. PMID: 26874559
- Boysen B G. Book Review: The Rat Brain in Stereotaxic Coordinates. J. Veterinary Pathology. 2008, 45(4):597-598. Google
- Hwee, D. T., Baehr, L. M., Philp, A., Baar, K. & Bodine, S. C. Maintenance of muscle mass and load-induced growth in Muscle RING Finger 1 null mice with age. Aging Cell. 2014, 13:92–101.PMID: 23941502
- Zhou Xiaoshuang, Li Rongshan,Liu Xinyan, Wang Lihua,Hui Peng, Chan Lawrence, Saha Pradip K, Hu Zhaoyong. ROCK1 reduces mitochondrial content and irisin production in muscle suppressing adipocyte browning and impairing insulin sensitivity. J. Scientific reports. 2016;6: 29669. PMID: 27411515
- Sousa—Ferreira L, Garrido M, Nascimento—Ferreira I. Moderate long-term modulation of neuropeptide Y in hypothalamic arcuate nucleus induces energy balance alterations in adult rats. J. PLoS One. 2011; 6(7): e22333. PMID: 21799827
- Santollo Jessica, Yao Dachun, Neal-Perry Genevieve, Etgen Anne M. Middle-aged female rats retain sensitivity to the anorexigenic effect of exogenous estradiol. J. Behavioural Brain Research. 2012 Jun 15;232(1):159-64. PMID: 22522024
- L.J. QIAO, Z. ZHENG, W.H. Ma. Effect of PUFA-containing diet on gut microbiota and fat metabolism-related genes in rats. Food Sci. 17 (2014) 231-235.
- Nicholls DG, Locke RM. Thermogeneic mechanisms in brown fat. Physol Rev. 1984,41:940-946. PMID: 6320232
- Zhang Y, Proenca R, Mafei M. et al. Positional cloning of the mouse obese gene and its human homologue. Nature. 1994, 372: 425-431. PMID: 7984236
Cite this Article:
International Journal of Sciences is Open Access Journal.
This article is licensed under a Creative Commons Attribution 4.0 International (CC BY 4.0) License.
Author(s) retain the copyrights of this article, though, publication rights are with Alkhaer Publications.