Abstract
Background: This study examined the effect of insulin sensitivity on the responsiveness of appetite regulatory brain regions to visual food cues.
Materials and methods: Nineteen participants diagnosed with polycystic ovary syndrome (PCOS) were divided into insulin-sensitive (n=8) and insulin-resistant (n=11) groups based on the homeostatic model assessment of insulin resistance (HOMA2-IR). Subjects underwent functional magnetic resonance imaging (fMRI) while viewing food pictures following water or dextrose consumption. The corticolimbic blood oxygen level dependent (BOLD) responses to high-calorie (HC) or low-calorie (LC) food pictures were compared within and between groups.
Results: BOLD responses to food pictures were reduced during a glucose challenge in numerous corticolimbic brain regions in insulin-sensitive but not insulin-resistant subjects. Furthermore, the degree of insulin resistance positively correlated with the corticolimbic BOLD response in the medial prefrontal cortex (mPFC), orbitofrontal cortex (OFC), anterior cingulate and ventral tegmental area (VTA) in response to HC pictures, and in the dorsolateral prefrontal cortex (DLPFC), mPFC, anterior cingulate, and insula in response to LC pictures following a glucose challenge. BOLD signal in the OFC, midbrain, hippocampus, and amygdala following a glucose challenge correlated with HOMA2-IR in response to HC-LC pictures.
Conclusion: We conclude that the normal inhibition of corticolimbic brain responses to food pictures during a glucose challenge is compromised in insulin-resistant subjects. The increase in brain responsiveness to food pictures during postprandial hyperinsulinemia may lead to greater non-homeostatic eating and perpetuate obesity in insulin-resistant subjects.
Acknowledgments
The authors wish to acknowledge financial support from Physicians Services Incorporated, Botterell Foundation, Canadian Foundation for Women’s Health, and King Saud Bin Abdulaziz University for Health Sciences.
References
1. Finkelstein EA, Trogdon JG, Cohen JW, Dietz W. Annual medical spending attributable to obesity: payer-and service-specific estimates. Health Aff (Millwood) 2009;28:w822–31.10.1377/hlthaff.28.5.w822Search in Google Scholar PubMed
2. Finkelstein EA, Khavjou OA, Thompson H, Trogdon JG, Pan L, Sherry B, Dietz W. Obesity and severe obesity forecasts through 2030. Am J Prev Med 2012;42:563–70.10.1016/j.amepre.2011.10.026Search in Google Scholar PubMed
3. Berthoud HR, Lenard NR, Shin AC. Food reward, hyperphagia, and obesity. Am J Physiol Regul Integr Comp Physiol 2011;300:R1266–77.10.1152/ajpregu.00028.2011Search in Google Scholar PubMed PubMed Central
4. Huerta CI, Sarkar PR, Duong TQ, Laird AR, Fox PT. Neural bases of food perception: coordinate-based meta-analyses of neuroimaging studies in multiple modalities. Obesity Res 2013;n/a.10.1002/oby.20659Search in Google Scholar PubMed PubMed Central
5. van der Laan LN, de Ridder DT, Viergever MA, Smeets PA. The first taste is always with the eyes: a meta-analysis on the neural correlates of processing visual food cues. Neuroimage 2011;55:296–303.10.1016/j.neuroimage.2010.11.055Search in Google Scholar PubMed
6. Siep N, Roefs A, Roebroeck A, Havermans R, Bonte ML, Jansen A. Hunger is the best spice: an fMRI study of the effects of attention, hunger and calorie content on food reward processing in the amygdala and orbitofrontal cortex. Behav Brain Res 2009;198:149–58.10.1016/j.bbr.2008.10.035Search in Google Scholar PubMed
7. Fuhrer D, Zysset S, Stumvoll M. Brain activity in hunger and satiety: an exploratory visually stimulated fMRI study. Obesity Res 2008;16:945–50.10.1038/oby.2008.33Search in Google Scholar PubMed
8. Stoeckel LE, Weller RE, Cook EW, III, Twieg DB, Knowlton RC, Cox JE. Widespread reward-system activation in obese women in response to pictures of high-calorie foods. Neuroimage 2008;41:636–47.10.1016/j.neuroimage.2008.02.031Search in Google Scholar PubMed
9. Rothemund Y, Preuschhof C, Bohner G, Bauknecht HC, Klingebiel R, Flor H, Klapp BF. Differential activation of the dorsal striatum by high-calorie visual food stimuli in obese individuals. Neuroimage 2007;37:410–21.10.1016/j.neuroimage.2007.05.008Search in Google Scholar PubMed
10. Martin LE, Holsen LM, Chambers RJ, Bruce AS, Brooks WM, Zarcone JR, Butler MG, Savage CR. Neural mechanisms associated with food motivation in obese and healthy weight adults. Obesity Res 2009;18:254–60.10.1038/oby.2009.220Search in Google Scholar PubMed
11. Holsen LM, Zarcone JR, Brooks WM, Butler MG, Thompson TI, Ahluwalia JS, Nollen NL, Savage CR. Neural mechanisms underlying hyperphagia in Prader-Willi Syndrome. Obesity Res 2006;14:1028–37.10.1038/oby.2006.118Search in Google Scholar
12. Schulingkamp RJ, Pagano TC, Hung D, Raffa RB. Insulin receptors and insulin action in the brain: review and clinical implications. Neurosci Biobehav Rev 2000;24:855–72.10.1016/S0149-7634(00)00040-3Search in Google Scholar
13. Baskin DG, Woods SC, West DB, van HM, Posner BI, Dorsa DM, Porte D, Jr. Immunocytochemical detection of insulin in rat hypothalamus and its possible uptake from cerebrospinal fluid. Endocrinology 1983;113:1818–25.10.1210/endo-113-5-1818Search in Google Scholar
14. Kleinridders A, Ferris HA, Cai W, Kahn CR. Insulin action in brain regulates systemic metabolism and brain function. Diabetes 2014;63:2232–43.10.2337/db14-0568Search in Google Scholar
15. Strubbe JH, Porte D, Woods SC. Insulin responses and glucose levels in plasma and cerebrospinal fluid during fasting and refeeding in the rat. Physiol Behav 1988;44:205–8.10.1016/0031-9384(88)90139-4Search in Google Scholar
16. Figlewicz DP, Sipols AJ, Seeley RJ, Chavez M, Woods SC, Porte D, Jr.: Intraventricular insulin enhances the meal-suppressive efficacy of intraventricular cholecystokinin octapeptide in the baboon. Behav Neurosci 1995;109:567–9.10.1037/0735-7044.109.3.567Search in Google Scholar
17. Woods SC, Lotter EC, McKay LD, Porte D, Jr.. Chronic intracerebroventricular infusion of insulin reduces food intake and body weight of baboons. Nature 1979;282:503–5.10.1038/282503a0Search in Google Scholar
18. Foster LA, Ames NK, Emery RS. Food intake and serum insulin responses to intraventricular infusions of insulin and IGF-I. Physiol Behav 1991;50:745–9.10.1016/0031-9384(91)90012-DSearch in Google Scholar
19. Hallschmid M, Higgs S, Thienel M, Ott V, Lehnert H. Postprandial administration of intranasal insulin intensifies satiety and reduces intake of palatable snacks in women. Diabetes 2012;61:782–9.10.2337/db11-1390Search in Google Scholar PubMed PubMed Central
20. Bruning JC, Gautam D, Burks DJ, Gillette J, Schubert M, Orban PC, Klein R, Krone W, Muller-Wieland D, Kahn CR. Role of brain insulin receptor in control of body weight and reproduction. Science 2000;289:2122–5.10.1126/science.289.5487.2122Search in Google Scholar PubMed
21. Wallner-Liebmann S, Koschutnig K, Reishofer G, Sorantin E, Blaschitz B, Kruschitz R, Unterrainer HF, Gasser R, Freytag F, Bauer-Denk C, Mangge H. Insulin and hippocampus activation in response to images of high-calorie food in normal weight and obese adolescents. Obesity Res 2010;18:1552–7.10.1038/oby.2010.26Search in Google Scholar PubMed
22. Guthoff M, Grichisch Y, Canova C, Tschritter O, Veit R, Hallschmid M, Haring HU, Preissl H, Hennige AM, Fritsche A. Insulin modulates food-related activity in the central nervous system. J Clin Endocrinol Metab 2010;95:748–55.10.1210/jc.2009-1677Search in Google Scholar PubMed
23. Kroemer NB, Krebs L, Kobiella A, Grimm O, Vollstadt-Klein S, Wolfensteller U, Kling R, Bidlingmaier M, Zimmermann US, Smolka MN. (Still) longing for food: Insulin reactivity modulates response to food pictures. Hum Brain Mapp 2012;n/a.10.1002/hbm.22071Search in Google Scholar PubMed PubMed Central
24. Lo JC, Feigenbaum SL, Yang J, Pressman AR, Selby JV, Go AS. Epidemiology and adverse cardiovascular risk profile of diagnosed polycystic ovary syndrome. J Clin Endocrinol Metab 2006;91:1357–63.10.1210/jc.2005-2430Search in Google Scholar PubMed
25. Dunaif A, Segal KR, Futterweit W, Dobrjansky A. Profound peripheral insulin resistance, independent of obesity, in polycystic ovary syndrome. Diabetes 1989;38:1165–74.10.2337/diab.38.9.1165Search in Google Scholar PubMed
26. Dunaif A. Insulin resistance and the polycystic ovary syndrome: mechanism and implications for pathogenesis. Endocr Rev 1997;18:774–800.10.1210/edrv.18.6.0318Search in Google Scholar
27. Amanti-Kandarakis E, Dunaif A. Insulin resistance and the polycystic ovary syndrome revisited: an update on mechanisms and implications. Endocr Rev 2012;33:981–1030.10.1210/er.2011-1034Search in Google Scholar PubMed PubMed Central
28. Moran LJ, Misso ML, Wild RA, Norman RJ. Impaired glucose tolerance, type 2 diabetes and metabolic syndrome in polycystic ovary syndrome: a systematic review and meta-analysis. Hum Reprod Update 2010;16:347–63.10.1093/humupd/dmq001Search in Google Scholar PubMed
29. Van Vugt DA, Krzemien A, Alsaadi H, Frank TC, Reid RL. Glucose-induced inhibition of the appetitive brain response to visual food cues in polycystic ovary syndrome patients. Brain Res 2014;1558:44–56.10.1016/j.brainres.2014.02.037Search in Google Scholar PubMed
30. PCOS Consensus Workshop Group. Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome (PCOS). Hum Reprod 2004; 19:41–7.10.1093/humrep/deh098Search in Google Scholar PubMed
31. Garner DM, Olmsted MP, Bohr Y, Garfinkel PE. The Eating Attitudes Test: psychometric features and clinical correlates. Psychol Med 1982;12:871–8.10.1017/S0033291700049163Search in Google Scholar PubMed
32. Marsh C, Berent-Spillson A, Love T, Persad CC, Pop-Busui R, Zubieta JK, Smith YR. Functional neuroimaging of emotional processing in women with polycystic ovary syndrome: a case-control pilot study. Fertil Steril 2013;100:200–7.10.1016/j.fertnstert.2013.02.054Search in Google Scholar
33. Worsley KJ, Friston KJ. Analysis of fMRI time-series revisited-again. Neuroimage 1995;2:173–81.10.1006/nimg.1995.1023Search in Google Scholar
34. Kroemer NB, Krebs L, Kobiella A, Grimm O, Vollstadt-Klein S, Wolfensteller U, Kling R, Bidlingmaier M, Zimmermann US, Smolka MN. (Still) longing for food: Insulin reactivity modulates response to food pictures. Hum Brain Mapp 2013;34:2367–80.10.1002/hbm.22071Search in Google Scholar
35. Vidarsdottir S, Smeets PA, Eichelsheim DL, van Osch MJ, Viergever MA, Romijn JA, Van der Grond J, Pijl H. Glucose ingestion fails to inhibit hypothalamic neuronal activity in patients with type 2 diabetes. Diabetes 2007;56:2547–50.10.2337/db07-0193Search in Google Scholar
36. Anthony K, Reed LJ, Dunn JT, Bingham E, Hopkins D, Marsden PK, Amiel SA. Attenuation of insulin-evoked responses in brain networks controlling appetite and reward in insulin resistance: the cerebral basis for impaired control of food intake in metabolic syndrome? Diabetes 2006;55:2986–92.10.2337/db06-0376Search in Google Scholar
37. Tschritter O, Preissl H, Hennige AM, Stumvoll M, Porubska K, Frost R, Marx H, Klosel B, Lutzenberger W, Birbaumer N, Haring HU, Fritsche A. The cerebrocortical response to hyperinsulinemia is reduced in overweight humans: a magnetoencephalographic study. Proc Natl Acad Sci USA 2006;103:12103–8.10.1073/pnas.0604404103Search in Google Scholar
38. Baskin DG, Figlewicz Lattemann D, Seeley RJ, Woods SC, Porte D, Jr., Schwartz MW. Insulin and leptin: dual adiposity signals to the brain for the regulation of food intake and body weight. Brain Res 1999;848:114–23.10.1016/S0006-8993(99)01974-5Search in Google Scholar
39. Korner J, Leibel RL. To eat or not to eat – how the gut talks to the brain. N Engl J Med 2003;349:926–8.10.1056/NEJMp038114Search in Google Scholar PubMed
40. Woods SC, Benoit SC, Clegg DJ. The brain-gut-islet connection. Diabetes 2006;55:S114–21.10.2337/db06-S015Search in Google Scholar
41. Woods SC, Figlewicz Lattemann DP, Schwartz MW, Porte D, Jr. A re-assessment of the regulation of adiposity and appetite by the brain insulin system. Int J Obes 1990;14 Suppl 3:69–73; discussion 74–6.:69–73.Search in Google Scholar
42. Page KA, Seo D, Belfort-DeAguiar R, Lacadie C, Dzuira J, Naik S, Amarnath S, Constable RT, Sherwin RS, Sinha R. Circulating glucose levels modulate neural control of desire for high-calorie foods in humans. J Clin Invest 2011;121:4161–9.10.1172/JCI57873Search in Google Scholar PubMed PubMed Central
43. van Golen LW, Veltman DJ, Ijzerman RG, Deijen JB, Heijboer AC, Barkhof F, Drent ML, Diamant M. Effects of insulin detemir and NPH insulin on body weight and appetite-regulating brain regions in human type 1 diabetes: a randomized controlled trial. PLoS One 2014;9:e94483.10.1371/journal.pone.0094483Search in Google Scholar PubMed PubMed Central
44. Killgore WD, Yurgelun-Todd DA. Body mass predicts orbitofrontal activity during visual presentations of high-calorie foods. Neuroreport 2005;16:859–63.10.1097/00001756-200505310-00016Search in Google Scholar PubMed
45. Frank TC, Kim GL, Krzemien A, Van Vugt DA. Effect of menstrual cycle phase on corticolimbic brain activation by visual food cues. Brain Res 2010;1363:81–92.10.1016/j.brainres.2010.09.071Search in Google Scholar PubMed
46. Van Vugt DA. Brain imaging studies of appetite in the context of obesity and the menstrual cycle. Hum Reprod Update 2010;16:276–92.10.1093/humupd/dmp051Search in Google Scholar PubMed
©2015 by De Gruyter
