Abstract
Approximately one-third of the world population is suffering from MetS, and the same is expected to rise in the years to come. Worldwide, most of the staple diets contain high amounts of carbohydrates, fats and comparatively low quantities of proteins. The goal of this study was to evaluate the effect of high fat-low protein diet in the development of the metabolic syndrome and associated cognitive deficits in the female rats. The rats fed with high fat-low protein diet (HFLPD) and 15% oral fructose solution for 24 weeks. Body weight, food intake, water intake, fasting blood glucose, oral glucose tolerance, glycosylated hemoglobin (HbA1C), and serum lipid profile were measured after every 4 weeks. Serum insulin, HOMA-IR index, rectal temperature, and systolic blood pressure were measured to confirm the manifestation of the hallmarks of metabolic syndrome. Behavioral tests for locomotion, anxiety, learning, and spatial memory were performed from the 12th week to till the end of the study. At the 24th week, oxidative stress assays and histopathology of liver, kidney, brain, and WAT were also performed. HFLPD significantly altered the physiologic and metabolic parameters which contributed to the manifestation of MetS. HFLPD also impaired the cognitive functions along with significant structural changes in the liver, kidney, WAT, and brain. The findings of this study reveal that HFLPD has the potential to induce the physiological, metabolic and histological alterations in rats, which eventually led to the development of MetS and also disrupted the cognitive functions in female rats.
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Abbreviations
- BAT:
-
Brown adipose tissue
- BMI:
-
Body mass index
- CD:
-
Cafeteria diet
- HbA1C :
-
Glycosylated hemoglobin
- HDL-c:
-
High-density lipoprotein cholesterol
- HFLPD:
-
High Fat-Low Protein Diet
- HOMA:
-
Homeostatic model assessment
- IR:
-
Insulin resistance
- LDL-c:
-
Low-density lipoprotein cholesterol
- MetS:
-
Metabolic syndrome
- MWM:
-
Morris water maze
- OFM:
-
Open field maze test
- T2DM:
-
Type 2 diabetes mellitus
- TC:
-
Total cholesterol
- TG:
-
Triglycerides
- TSTQ:
-
Time spent in target quadrant
- WD:
-
Western diet
References
Alberti KGMM, Zimmet P, Shaw J (2005) The metabolic syndrome—a new worldwide definition. Lancet 366:1059–1062
Asai A, Miyazawa T (2001) Dietary curcuminoids prevent high-fat diet-induced lipid accumulation in rat liver and epididymal adipose tissue. J Nutr 131:2932–2935
Bansal Y, Singh R, Saroj P, Sodhi RK, Kuhad A (2018) Naringenin protects against oxido-inflammatory aberrations and altered tryptophan metabolism in olfactory bulbectomized-mice model of depression. Toxicol Appl Pharmacol 355:257–268. https://doi.org/10.1016/J.TAAP.2018.07.010
Buettner R, Buettner R (2016) High-fat Diets: modeling the metabolic disorders of human obesity in Rodents * High-fat Diets : Modeling the Metabolic Disorders of Human Obesity in Rodents. 15:. https://doi.org/10.1038/oby.2007.608
Cani PEA (2008) Changes in gut microbiota control metabolic endotoxemia-induced inflammation in high-fat diet-induced obesity and diabetes in mice. Diabetes 57:1470–1481
Cani PD, Amar J, Iglesias MA, Poggi M, Knauf C, Bastelica D, Neyrinck AM, Fava F, Tuohy KM, Chabo C, Waget A, Delmee E, Cousin B, Sulpice T, Chamontin B, Ferrieres J, Tanti JF, Gibson GR, Casteilla L, Delzenne NM, Alessi MC, Burcelin R (2007) Original Article. Diabetes 56:1761–1772. https://doi.org/10.2337/db06-1491.P.D.C
Convit A (2005) Links between cognitive impairment in insulin resistance: an explanatory model. Neurobiol Aging 26:31–35
Cordner ZA, Tamashiro KLK (2015) Effects of high-fat diet exposure on learning & memory. Physiol Behav 152:363–371. https://doi.org/10.1016/j.physbeh.2015.06.008
Diabetes Atlas I (2017) The IDF diabetes Atlas , 8th edition country report 2017 & 2045 Prevalence of diabetes compared to other countries , 2017 Brazil At a Glance
Doddigarla Z, Ahmad J, Parwez I (2016) Effect of chromium picolinate and melatonin either in single or in a combination in high carbohydrate diet-fed male Wistar rats. BioFactors 42:106–114. https://doi.org/10.1002/biof.1253
Eyres L, Eyres MF, Chisholm A, Brown RC (2016) Coconut oil consumption and cardiovascular risk factors in humans. Nutr Rev 74:267–280. https://doi.org/10.1093/nutrit/nuw002
Francis H, Stevenson R (2013) The longer-term impacts of Western diet on human cognition and the brain. Appetite 63:119–128. https://doi.org/10.1016/j.appet.2012.12.018
Freeman LR, Haley-Zitlin V, Rosenberger DS, Granholm A-C (2014) Damaging effects of a high-fat diet to the brain and cognition: a review of proposed mechanisms. Nutr Neurosci 17:241–251. https://doi.org/10.1179/1476830513Y.0000000092
Greenwood CE, Winocur G (2005) High-fat diets, insulin resistance and declining cognitive function. In: Neurobiology of Aging
Gregg EW, Yaffe K, Cauley JA et al (2000) Is diabetes associated with cognitive impairment and cognitive decline among older women? Arch Intern Med 160:174–180
Grundy SM (2008) Metabolic syndrome pandemic. Arterioscler Thromb Vasc Biol 28:629–636
Grundy SM, Brewer HB Jr, Cleeman JI et al (2004) Definition of metabolic syndrome: report of the National Heart, Lung, and Blood Institute/American Heart Association conference on scientific issues related to definition. Circulation 109:433–438
Gunathilake R, Oldmeadow C, McEvoy M, Inder KJ, Schofield PW, Nair BR, Attia J (2016) The association between obesity and cognitive function in older persons: how much is mediated by inflammation, fasting plasma glucose, and hypertriglyceridemia? J Gerontol Ser A Biomed Sci Med Sci 71:1603–1608
Hall J, Juncos L, Wang Z, Hall M, do Carmo J, da Silva A (2014) Obesity, hypertension, and chronic kidney disease. Int J Nephrol Renov Dis 7:75. https://doi.org/10.2147/IJNRD.S39739
Hamsi MA, Othman F, Das S, Kamisah Y, Thent ZC, Qodriyah HMS, Zakaria Z, Emran A, Subermaniam K, Jaarin K (2015) Effect of consumption of fresh and heated virgin coconut oil on the blood pressure and inflammatory biomarkers: an experimental study in Sprague Dawley rats. Alex J Med 51:53–63. https://doi.org/10.1016/j.ajme.2014.02.002
Hariri N, Thibault L (2010) High-fat diet-induced obesity in animal models. Nutr Res Rev 23:270–299. https://doi.org/10.1017/S0954422410000168
Holloway CJ, Cochlin LE, Emmanuel Y, Murray A, Codreanu I, Edwards LM, Szmigielski C, Tyler DJ, Knight NS, Saxby BK, Lambert B, Thompson C, Neubauer S, Clarke K (2011) A high-fat diet impairs cardiac high-energy phosphate metabolism and cognitive function in healthy human subjects. Am J Clin Nutr 93:748–755. https://doi.org/10.3945/ajcn.110.002758
Hopps E, Noto D, Caimi G, Averna MR (2010) REVIEW a novel component of the metabolic syndrome : the oxidative stress. Nutr Metab Cardiovasc Dis 20:72–77. https://doi.org/10.1016/j.numecd.2009.06.002
https://www.statista.com (2018) No Title. https://www.statista.com/outlook/20020000/119/soft-drinks/india. Accessed 3 March 2018
Jiang T, Wang Z, Proctor G, Moskowitz S, Liebman SE, Rogers T, Lucia MS, Li J, Levi M (2005) Diet-induced obesity in C57BL/6J mice causes increased renal lipid accumulation and glomerulosclerosis via a sterol regulatory element-binding protein-1c-dependent pathway. J Biol Chem 280:32317–32325. https://doi.org/10.1074/jbc.M500801200
Jollow DJ, Mitchell JR, al ZN, Gillette JR (1974) Bromobenzene-induced liver necrosis. Protective role of glutathione and evidence for 3, 4-bromobenzene oxide as the hepatotoxic metabolite. Pharmacology 11:151–169
Kanoski SE, Davidson TL (2011) Western diet consumption and cognitive impairment: links to hippocampal dysfunction and obesity. Physiol Behav 103:59–68. https://doi.org/10.1016/j.physbeh.2010.12.003
Kaur J (2014) A comprehensive review on metabolic syndrome. Cardiol Res Pract 2014:1–21
Kim KA, Gu W, Lee IA, Joh EH, Kim DH (2012) High fat diet-induced gut microbiota exacerbates inflammation and obesity in mice via the TLR4 signaling pathway. PLoS One 7:e47713. https://doi.org/10.1371/journal.pone.0047713
Kohsaka A, Laposky AD, Ramsey KM, Estrada C, Joshu C, Kobayashi Y, Turek FW, Bass J (2007) High-fat diet disrupts behavioral and molecular circadian rhythms in mice. Cell Metab 6:414–421. https://doi.org/10.1016/j.cmet.2007.09.006
Kono Y (1978) Generation of superoxide radical during autoxidation of hydroxylamine and an assay for superoxide dismutase. Arch Biochem Biophys 186:189–195
Kothari V, Luo Y, Tornabene T, O'Neill AM, Greene MW, Geetha T, Babu JR (2017) High fat diet induces brain insulin resistance and cognitive impairment in mice. Biochim Biophys Acta Mol basis Dis 1863:499–508. https://doi.org/10.1016/j.bbadis.2016.10.006
Kulkarni NM, Jaji MS, Shetty P, Kurhe YV, Chaudhary S, Vijaykant G, Raghul J, Vishwakarma SL, Rajesh BN, Mookkan J, Krishnan UM, Narayanan S (2015) A novel animal model of metabolic syndrome with non-alcoholic fatty liver disease and skin inflammation. Pharm Biol 53:1110–1117. https://doi.org/10.3109/13880209.2014.960944
Kumar A, Sehgal N, Kumar P et al (2008) Protective effect of quercetin against ICV colchicine-induced cognitive dysfunctions and oxidative damage in rats. Phytother Res 22:1563–1569
Li N, Fu J, Koonen DP, Kuivenhoven JA, Snieder H, Hofker MH (2014) Are hypertriglyceridemia and low HDL causal factors in the development of insulin resistance? Atherosclerosis 233:130–138
Matova EE, Vihert AM (1976) Atherosclerosis and hypertension. Bull World Health Organ 53:539–546. https://doi.org/10.1097/00005344-199000005-00009
Matsuda M, Shimomura I (2013) Increased oxidative stress in obesity: implications for metabolic syndrome , diabetes, hypertension, dyslipidemia, atherosclerosis, and cancer. Obes Res Clin Pract 1–12. https://doi.org/10.1016/j.orcp.2013.05.004, 7
Meng X, Zou D, Shi Z, Duan Z, Mao Z (2004) Dietary diacylglycerol prevents high-fat diet-induced lipid accumulation in rat liver and abdominal adipose tissue. Lipids 39:37–41. https://doi.org/10.1007/s11745-004-1199-1
Murtaza N, Baboota RK, Jagtap S, Singh DP, Khare P, Sarma SM, Podili K, Alagesan S, Chandra TS, Bhutani KK, Boparai RK, Bishnoi M, Kondepudi KK (2014) Finger millet bran supplementation alleviates obesity-induced oxidative stress, inflammation and gut microbial derangements in high-fat diet-fed mice. Br J Nutr 112:1447–1458
Noeman SA, Hamooda HE, Baalash AA (2011) Biochemical study of oxidative stress markers in the liver , kidney and heart of high fat diet induced obesity in rats. 1–8
Panchal SK, Poudyal H, Iyer A et al (2011) High-carbohydrate , high-fat diet – induced metabolic syndrome and cardiovascular remodeling in rats. J Cardiovasc Pharmacol 57:611–624
Pistell PJ, Morrison CD, Gupta S, Knight AG, Keller JN, Ingram DK, Bruce-Keller AJ (2010) Cognitive impairment following high fat diet consumption is associated with brain inflammation. J Neuroimmunol 219:25–32
Poppitt SD, Keogh GF, Prentice AM, Williams DEM, Sonnemans HMW, Valk EEJ, Robinson E, Wareham NJ (2002) Long-term effects of ad libitum low-fat, high-carbohydrate diets on body weight and serum lipids in overweight subjects with metabolic syndrome. Am J Clin Nutr 75:11–20
Ranasinghe P, Mathangasinghe Y, Jayawardena R, Hills AP, Misra A (2017) Prevalence and trends of metabolic syndrome among adults in the asia-pacific region: a systematic review. BMC Public Health 17:101
Report WN (2014) World Health Organization, noncommunicable diseases country profiles 2014, WHO Library Cataloguing-in-Publication Data, Geneva, Switzerland, 2014. https://doi.org/10.1111/jgs.12171
Roberts CK, Sindhu KK (2009) Oxidative stress and metabolic syndrome. Life Sci 84:705–712. https://doi.org/10.1016/j.lfs.2009.02.026
Sachdeva AK, Dharavath RN, Chopra K (2018) Time-response studies on development of cognitive deficits in an experimental model of insulin resistance. Clin Nutr 1–10. https://doi.org/10.1016/j.clnu.2018.06.966
Schwingshackl L, Bogensberger B, Bencic A et al (2018) Effects of oils and solid fats on blood lipids: a systematic review and network meta-analysis. J Lipid Res 59:jlr.P085522. https://doi.org/10.1194/jlr.P085522
Shankar P, Sundarka M (2010) Misery of human Cupiditas: material characteristics. J Indian Acad Clin Med 2:275–281
Singh DP, Singh J, Boparai RK, Zhu JH, Mantri S, Khare P, Khardori R, Kondepudi KK, Chopra K, Bishnoi M (2017) Isomalto-oligosaccharides, a prebiotic, functionally augment green tea effects against high fat diet-induced metabolic alterations via preventing gut dysbacteriosis in mice. Pharmacol Res 123:103–113
Souza CG, Moreira JD, Siqueira IR, Pereira AG, Rieger DK, Souza DO, Souza TM, Portela LV, Perry MLS (2007) Highly palatable diet consumption increases protein oxidation in rat frontal cortex and anxiety-like behavior. Life Sci 81:198–203. https://doi.org/10.1016/j.lfs.2007.05.001
Spence RD, Voskuhl RR (2012) Neuroprotective effects of estrogens and androgens in CNS inflammation and neurodegeneration. Front Neuroendocrinol 33:105–115
Underwood EL, Thompson LT (2016) A high-fat diet causes impairment in hippocampal memory and sex-dependent alterations in peripheral metabolism. Neural Plast 2016:1–10. https://doi.org/10.1155/2016/7385314
Wang J, Jiang C, Liu C, Li X, Chen N, Hao Y (2010) Neuroprotective effects of progesterone following stroke in aged rats. Behav Brain Res 209:119–122
Wei-Chuan Tsai, Yi-Heng Li, Chih-Chan Lin, Ting-Hsing Chao, Jyh-Hong Chen (2004) Effects of oxidative stress on endothelial function after a high-fat meal. Clin Sci 106(3):315–319
White CL, Pistell PJ, Purpera MN, Gupta S, Fernandez-Kim SO, Hise TL, Keller JN, Ingram DK, Morrison CD, Bruce-Keller AJ (2009) Effects of high fat diet on Morris maze performance, oxidative stress, and inflammation in rats: contributions of maternal diet. Neurobiol Dis 35:3–13. https://doi.org/10.1016/j.nbd.2009.04.002
Wills ED (1966) Mechanisms of lipid peroxide formation in animal tissues. Biochem J 99:667–676
Winocur G, Greenwood CE (2005) Studies of the effects of high fat diets on cognitive function in a rat model. Neurobiol Aging 26:46–49
Wood R, Kubena K, O’Brien B et al (1993) Effect of butter, mono- and polyunsaturated fatty acid-enriched butter, trans fatty acid margarine, and zero trans fatty acid margarine on serum lipids and lipoproteins in healthy men. J Lipid Res 34:1–11
Acknowledgments
The authors duly acknowledge the University Grants Commission, New Delhi, India for providing UGC-BSR-RFSMS fellowship to Ravinder Naik Dharavath and Panjab University, Chandigarh for providing research facilities.
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RND, KC, MB, and KKK had conceived the idea and designed the study. RND & SA did the experimental work, data collection, data analysis, and manuscript preparation. KC, MB, and KKK reviewed and revised the manuscript.
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Dharavath, R.N., Arora, S., Bishnoi, M. et al. High fat-low protein diet induces metabolic alterations and cognitive dysfunction in female rats. Metab Brain Dis 34, 1531–1546 (2019). https://doi.org/10.1007/s11011-019-00459-4
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DOI: https://doi.org/10.1007/s11011-019-00459-4