Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Article
  • Published:

Animal Models

Effects of central administration of distinct fatty acids on hypothalamic neuropeptide expression and energy metabolism

International Journal of Obesity volume 35, pages 336–344 (2011)Cite this article

Subjects

Abstract

Objective:

To investigate the differential effects of acute central administration of distinct fatty acids (FA) on food intake, body weight and energy metabolism.

Design:

Male Sprague–Dawley rats were treated with bolus intracerebroventricular injections of control hydroxypropyl-β-cyclodextrin (HPB) or HPB complexed with 30 nmol of saturated palmitic acid (PA), monounsaturated oleic acid (OA) or polyunsaturated ω-3 docosahexaenoic acid (DHA). Food intake, body weight, neuropeptide expression and various serum parameters were assessed.

Results:

When compared with controls, rats injected with either OA or DHA had significantly reduced food intake and body weight for 48 h following injections. No significant changes in food intake or body weight were observed in the PA group. In conjunction with reduced food intake, hypothalamic anorexigenic pro-opiomelanocortin (POMC) gene expression was significantly augmented in the OA and DHA groups, with essentially no changes observed in the PA group. Changes in serum measures of energy metabolism also changed coinciding with the observed differences in food intake. Moreover, central administration of SHU9119, a melanocortin-4-rececptor (MC4R) antagonist, completely abolished the anorexigenic actions of OA, suggesting a role for OA-induced augmentation of hypothalamic POMC expression in mediating its central inhibition of food intake.

Conclusions:

The hypothalamus differentially senses FA and, specifically, that OA and DHA, but not PA, reduce food intake and body weight, which may be mediated through POMC/MC4R signaling.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5

Similar content being viewed by others

References

  1. Adan RA, Tiesjema B, Hillebrand JJ, la Fleur SE, Kas MJ, de Krom M . The MC4 receptor and control of appetite. Br J Pharmacol 2006; 149: 815–827.

    Article  CAS  Google Scholar 

  2. Seeley RJ, Drazen DL, Clegg DJ . The critical role of the melanocortin system in the control of energy balance. Annu Rev Nutr 2004; 24: 133–149.

    Article  CAS  Google Scholar 

  3. Vergoni AV, Bertolini A . Role of melanocortins in the central control of feeding. Eur J Pharmacol 2000; 405: 25–32.

    Article  CAS  Google Scholar 

  4. Lee M, Wardlaw SL . The central melanocortin system and the regulation of energy balance. Front Biosci 2007; 12: 3994–4010.

    Article  CAS  Google Scholar 

  5. Chee MJ, Colmers WF . Y eat? Nutrition 2008; 24: 869–877.

    Article  CAS  Google Scholar 

  6. Coll AP . Effects of pro-opiomelanocortin (POMC) on food intake and body weight: mechanisms and therapeutic potential? Clin Sci (Lond) 2007; 113: 171–182.

    Article  CAS  Google Scholar 

  7. Ilnytska O, Argyropoulos G . The role of the Agouti-Related Protein in energy balance regulation. Cell Mol Life Sci 2008; 65: 2721–2731.

    Article  CAS  Google Scholar 

  8. Cota D, Proulx K, Seeley RJ . The role of CNS fuel sensing in energy and glucose regulation. Gastroenterology 2007; 132: 2158–2168.

    Article  CAS  Google Scholar 

  9. Le Foll C, Irani BG, Magnan C, Dunn-Meynell AA, Levin BE . Characteristics and mechanisms of hypothalamic neuronal fatty acid sensing. Am J Physiol Regul Integr Comp Physiol 2009; 297: R655–R664.

    Article  CAS  Google Scholar 

  10. Moran TH . Hypothalamic nutrient sensing and energy balance. Forum Nutr 2010; 63: 94–101.

    Article  CAS  Google Scholar 

  11. Lam TK, Schwartz GJ, Rossetti L . Hypothalamic sensing of fatty acids. Nat Neurosci 2005; 8: 579–584.

    Article  CAS  Google Scholar 

  12. Lopez M, Tovar S, Vazquez MJ, Nogueiras R, Senaris R, Dieguez C . Sensing the fat: fatty acid metabolism in the hypothalamus and the melanocortin system. Peptides 2005; 26: 1753–1758.

    Article  CAS  Google Scholar 

  13. Chakravarthy MV, Zhu Y, Yin L, Coleman T, Pappan KL, Marshall CA et al. Inactivation of hypothalamic FAS protects mice from diet-induced obesity and inflammation. J Lipid Res 2009; 50: 630–640.

    Article  CAS  Google Scholar 

  14. Lane MD, Wolfgang M, Cha SH, Dai Y . Regulation of food intake and energy expenditure by hypothalamic malonyl-CoA. Int J Obes (Lond) 2008; 32 (Suppl 4): S49–S54.

    Article  CAS  Google Scholar 

  15. Pocai A, Lam TK, Obici S, Gutierrez-Juarez R, Muse ED, Arduini A et al. Restoration of hypothalamic lipid sensing normalizes energy and glucose homeostasis in overfed rats. J Clin Invest 2006; 116: 1081–1091.

    Article  CAS  Google Scholar 

  16. Wolfgang MJ, Cha SH, Millington DS, Cline G, Shulman GI, Suwa A et al. Brain-specific carnitine palmitoyl-transferase-1c: role in CNS fatty acid metabolism, food intake, and body weight. J Neurochem 2008; 105: 1550–1559.

    Article  CAS  Google Scholar 

  17. Obici S, Feng Z, Morgan K, Stein D, Karkanias G, Rossetti L . Central administration of oleic acid inhibits glucose production and food intake. Diabetes 2002; 51: 271–275.

    Article  CAS  Google Scholar 

  18. Jo YH, Su Y, Gutierrez-Juarez R, Chua Jr S . Oleic acid directly regulates POMC neuron excitability in the hypothalamus. J Neurophysiol 2009; 101: 2305–2316.

    Article  CAS  Google Scholar 

  19. Benoit SC, Kemp CJ, Elias CF, Abplanalp W, Herman JP, Migrenne S et al. Palmitic acid mediates hypothalamic insulin resistance by altering PKC-theta subcellular localization in rodents. J Clin Invest 2009; 119: 2577–2589.

    Article  CAS  Google Scholar 

  20. Milanski M, Degasperi G, Coope A, Morari J, Denis R, Cintra DE et al. Saturated fatty acids produce an inflammatory response predominantly through the activation of TLR4 signaling in hypothalamus: implications for the pathogenesis of obesity. J Neurosci 2009; 29: 359–370.

    Article  CAS  Google Scholar 

  21. Dziedzic B, Szemraj J, Bartkowiak J, Walczewska A . Various dietary fats differentially change the gene expression of neuropeptides involved in body weight regulation in rats. J Neuroendocrinol 2007; 19: 364–373.

    Article  CAS  Google Scholar 

  22. Huang XF, Xin X, McLennan P, Storlien L . Role of fat amount and type in ameliorating diet-induced obesity: insights at the level of hypothalamic arcuate nucleus leptin receptor, neuropeptide Y and pro-opiomelanocortin mRNA expression. Diabetes Obes Metab 2004; 6: 35–44.

    Article  CAS  Google Scholar 

  23. Hill AM, Buckley JD, Murphy KJ, Howe PR . Combining fish-oil supplements with regular aerobic exercise improves body composition and cardiovascular disease risk factors. Am J Clin Nutr 2007; 85: 1267–1274.

    Article  CAS  Google Scholar 

  24. Wang H, Storlien LH, Huang XF . Effects of dietary fat types on body fatness, leptin, and ARC leptin receptor, NPY, and AGRP mRNA expression. Am J Physiol Endocrinol Metab 2002; 282: E1352–E1359.

    Article  CAS  Google Scholar 

  25. Roche HM, Gibney MJ . Long-chain n-3 polyunsaturated fatty acids and triacylglycerol metabolism in the postprandial state. Lipids 1999; 34 (Suppl): S259–S265.

    Article  CAS  Google Scholar 

  26. Sampath H, Ntambi JM . Polyunsaturated fatty acid regulation of genes of lipid metabolism. Annu Rev Nutr 2005; 25: 317–340.

    Article  CAS  Google Scholar 

  27. Bergouignan A, Momken I, Schoeller DA, Simon C, Blanc S . Metabolic fate of saturated and monounsaturated dietary fats: the Mediterranean diet revisited from epidemiological evidence to cellular mechanisms. Prog Lipid Res 2009; 48: 128–147.

    Article  CAS  Google Scholar 

  28. Riccardi G, Giacco R, Rivellese AA . Dietary fat, insulin sensitivity and the metabolic syndrome. Clin Nutr 2004; 23: 447–456.

    Article  CAS  Google Scholar 

  29. van Dijk SJ, Feskens EJ, Bos MB, Hoelen DW, Heijligenberg R, Bromhaar MG et al. A saturated fatty acid-rich diet induces an obesity-linked proinflammatory gene expression profile in adipose tissue of subjects at risk of metabolic syndrome. Am J Clin Nutr 2009; 90: 1656–1664.

    Article  CAS  Google Scholar 

  30. Buggy J, Hoffman WE, Phillips MI, Fisher AE, Johnson AK . Osmosensitivity of rat third ventricle and interactions with angiotensin. Am J Physiol 1979; 236: R75–R82.

    CAS  PubMed  Google Scholar 

  31. Yaksh TL, Jang JD, Nishiuchi Y, Braun KP, Ro SG, Goodman M . The utility of 2-hydroxypropyl-beta-cyclodextrin as a vehicle for the intracerebral and intrathecal administration of drugs. Life Sci 1991; 48: 623–633.

    Article  CAS  Google Scholar 

  32. Adage T, Scheurink AJ, de Boer SF, de Vries K, Konsman JP, Kuipers F et al. Hypothalamic, metabolic, and behavioral responses to pharmacological inhibition of CNS melanocortin signaling in rats. J Neurosci 2001; 21: 3639–3645.

    Article  CAS  Google Scholar 

  33. Boghossian S, Park M, York DA . Melanocortin activity in the amygdala controls appetite for dietary fat. Am J Physiol Regul Integr Comp Physiol 2010; 298: R385–R393.

    Article  CAS  Google Scholar 

  34. Morgan K, Obici S, Rossetti L . Hypothalamic responses to long-chain fatty acids are nutritionally regulated. J Biol Chem 2004; 279: 31139–31148.

    Article  CAS  Google Scholar 

  35. Velloso LA, Araujo EP, de Souza CT . Diet-induced inflammation of the hypothalamus in obesity. Neuroimmunomodulation 2008; 15: 189–193.

    Article  CAS  Google Scholar 

  36. Lam TK, Pocai A, Gutierrez-Juarez R, Obici S, Bryan J, Aguilar-Bryan L et al. Hypothalamic sensing of circulating fatty acids is required for glucose homeostasis. Nat Med 2005; 11: 320–327.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We thank Martha Grace for her excellent technical support and Anaya Mitra for assistance with surgeries. These studies were supported by a pilot and feasibility Grant from the Minnesota Obesity Center (NIDDK P30DK50546) and from a Grant-in-Aid from the University of Minnesota Graduate School to DG Mashek, and from the National Institute on Drug Abuse (R01DA021280) to BA Gosnell.

Author information

Authors and Affiliations

  1. Department of Food Science and Nutrition, University of Minnesota, St Paul, MN, USA

    D R Schwinkendorf, N G Tsatsos, B A Gosnell & D G Mashek

Authors
  1. D R Schwinkendorf
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. N G Tsatsos
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. B A Gosnell
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. D G Mashek
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to D G Mashek.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Schwinkendorf, D., Tsatsos, N., Gosnell, B. et al. Effects of central administration of distinct fatty acids on hypothalamic neuropeptide expression and energy metabolism. Int J Obes 35, 336–344 (2011). https://doi.org/10.1038/ijo.2010.159

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/ijo.2010.159

Keywords

This article is cited by

Search

Advanced search

Quick links