Body Weight, Insulin Resistance, and Inflammatory Biomarkers in Rats Fed Normal-Fat, High-Fat, and Ketogenic Diets Supplemented with Vitamin D
DOI:
https://doi.org/10.35516/jjas.v17i1.64Keywords:
Carbohydrate, Bodyweight, Insulin resistance, High-fat diet, Ketogenic diet, Obesity, Rat, Vitamin DAbstract
Ketogenic (KD) and high-fat (HFD) diets and vitamin D (VD) produce variable effects on insulin secretion and body weight (BW), but mechanisms remain unclear. We investigated the effects of normal fat diets (NFD), KD, and HFD with and without VD on BW and serum glucose, insulin, VD, insulin resistance, C-reactive protein, interleukin-6, and tumor necrosis factor-alpha in rats. Three isocaloric NFD, KD, and HFD containing respectively protein-carbohydrate-fat (NFD: 14.8%-75.7%-9.5%; KD:20.2%-10.3%-69.5%; HFD:15.2%-42.7-42.0%) and three other similar diets but with (1000 IU/kg) VD were used. Forty-five adult male Sprague-Dawley rats were used, 5 rats were sacrificed at the start, remainders were randomly divided into NFD (n=15) and HFD (n=25), and fed for 8 weeks, then 5 rats from each were sacrificed. NFD remainders were divided into 2 subgroups (n=5) and fed NFD and NFD-VD, and HFD remainders were divided into 4 subgroups (n=5) and fed HFD, HFD-VD, KD, and KD-VD for further 8 weeks, then all rats were sacrificed. BW and food intake were measured, food conversion ratio (FCR) was calculated, and biological variables were determined following standard protocols. BW change and FCR (-15.6± -10.13g; 0.033±0.350 respectively) of rats fed KD-VD were the lowest (P<0.05) compared to those fed KD (144.8±1.47g; 0.189±0.050), HFD-VD (143.0±8.49g; 0.187±0.100), HFD (155.8±0.3g; 0.203±0.010), NFD-VD (142.8±6.34g; 0.183±0.009), and NFD (51.0±1.02g; 0.074±0.110) respectively. BW change correlated (P<0.01) with food intake (r=0.752), % carbohydrate (r=0.292), and % fat (r=0.341). None of the diets affected other biomarkers. Results clearly show BW-reducing effects for KD-VD that may be mediated by changes in food intake and dietary fat and carbohydrate proportion.
Downloads
References
Ahmad M.N., Al-Badarein B.O. (2019). Analysis of evidence linking dietary carbohydrate and fat proportions with body weight and insulin resistance. International Journal of Applied and Natural Sciences. 8(6): 43-60.
Afzal S., Bojesen S.E., Nordestgaard B.G. (2013). Low 25-hydroxyvitamin D and risk of type 2 diabetes: a prospective cohort study and meta-analysis. Clinical Chemistry, 59(2): 381–91.
Afzal S., Brøndum-Jacobsen P., Bojesen S.E., Nordestgaard B.G. (2014). Vitamin D of diabetes: A mendelian randomization study. Lancet Diabetes Endocrinology, 2(4): 298–306.
Ajlouni K., Khader Y., Batieha A., Jaddou H., El-Khateeb M. (2020). An alarmingly high and increasing prevalence of obesity in Jordan. Epidemiology and Health, 42: e2020040.
Aloia J.F., Patel M., DiMaano R., Li-Ng M., Talwar S.A., Mikhail M., et al. (2008). Vitamin D intake to attain a desired serum 25-hydroxyvitamin D concentration. American Journal of Clinical Nutrition, 87(6): 1952–8.
Asrih M., Altirriba J., Rohner-Jeanrenaud F., Jornayvaz F.R. (2015). A ketogenic diet impairs FGF21 signaling and promotes differential inflammatory responses in the liver and white adipose tissue. PLoS One, 10(5): e0126364.
Awazawa M., Ueki K., Inabe K., Yamauchi T., Kubota N., Kaneko K., et al. (2011). Adiponectin enhances insulin sensitivity by increasing hepatic IRS-2 expression via a macrophage-derived IL-6-dependent pathway. Cell Metabolism, 13(4): 401–12.
Aylward N.M., Shah N., Sellers E.A. (2014). The ketogenic diet for the treatment of myoclonic-astatic epilepsy in a child with type 1 diabetes mellitus. Canadian Journal of Diabetes, 38(4): 223-4.
Badman M.K., Kennedy A.R., Adams A.C., Pissios P., Maratos-Flier E. (2009). A very low carbohydrate ketogenic diet improves glucose tolerance in ob/ob mice independently of weight loss. American Journal of Physiology, Endocrinology, and Metabolism, 297(5): E1197-204.
Balvers M.G.J., Verhoeckx K.C.M., Meijerink J., Bijlsma S., Rubingh C.M., Wortelboer H.M., et al. (2015). Time-dependent effect of in vivo inflammation on eicosanoid and endocannabinoid levels in plasma, liver, ileum, and adipose tissue in C57BL/6 mice fed a fish-oil diet. Int Immunopharmacology, 13(2): 204–14.
Barger-Lux M.J., Heaney R.P., Dowell S., Chen T.C., Holick M.F. (1998). Vitamin D and its major metabolites: serum levels after graded oral dosing in healthy men. Osteoporosis International, 8(3): 222–30.
Bergqvist A.G.C., Schall J.I., Stallings V.A., Zemel BS. (2008). Progressive bone mineral content loss in children with intractable epilepsy treated with the ketogenic diet. American Journal of Clinical Nutrition, 88(6): 1678–84.
Bielohuby M., Sisley S., Sandoval D., Herbach N., Zengin A., Fischereder M., et al. (2013). Impaired glucose tolerance in rats fed low-carbohydrate, high-fat diets. American Journal of Physiology, Endocrinology, and Metabolism, 305(9): E1059–70.
Blok W.L., Deslypere J-P., Demacker P.N.M., Van Der Ven-Jongekrijg J., Hectors M.P.C., Van Der Meer J.W.M., et al. (1997). Pro- and anti-inflammatory cytokines in healthy volunteers fed various doses of fish oil for 1 year. European Journal of Clinical Investigation, 27(12): 1003–8.
Bradley L.E., Forman E.M., Kerrigan S.G., Goldstein S.P., Butryn M.L., Thomas J.G., et al. (2017). Project HELP: A remotely delivered behavioral intervention for weight regains after bariatric surgery. Obesity Surgery, 27(3): 586–98.
Brouwer D.A., van Beek J., Ferwerda H., Brugman A.M., van der Klis F.R., van der Heiden H.J., et al. (1998). Rat adipose tissue rapidly accumulates and slowly releases an orally administered high vitamin D dose. British Journal of Nutrition, 79(6): 527–32.
Burcelin R., Crivelli V., Dacosta A., Roy-Tirelli A., Thorens B. (2002). Heterogeneous metabolic adaptation of C57BL/6J mice to a high-fat diet. American Journal of Physiology, Endocrinology, and Metabolism, 282(4): E834-42.
Caron-Jobin M., Morisset A-S., Tremblay A., Huot C., Légaré D., Tchernof A. (2011). Elevated serum 25(OH)D concentrations, vitamin D, and calcium intakes are associated with reduced adipocyte size in women. Obesity (Silver Spring), 19(7): 1335–41.
Cheng S., Massaro J.M., Fox C.S., Larson M.G., Keyes M.J., McCabe E.L., et al. (2010). Adiposity, cardiometabolic risk, and vitamin D status: the Framingham Heart Study. Diabetes, 59(1): 242–8.
Clark M.J., Slavin J.L. (2013). The effect of fiber on satiety and food intake: A systematic review. Journal of American College of Nutrition, 32(3): 200–11.
Clement, T.E., Cahoon, E.B. (2009). Soybean oil: genetic approaches for modification of functionality and total content. Plant Physiology, 151(3): 1030-1040.
Cooper A.L., Gibbons L., Horan M.A., Little R.A., Rothwell N.J. (1993). Effect of dietary fish oil supplementation on fever and cytokine production in human volunteers. Clinical Nutrition, 12(6): 321–8.
Cummins T.D., Holden C.R., Sansbury B.E., Gibb A.A., Shah J., Zafar N., et al. (2014). Metabolic remodeling of white adipose tissue in obesity. American Journal of Physiology, Endocrinology, and Metabolism, 307(3): E262–77.
Douris N., Melman T., Pecherer J.M., Pissios P., Flier J.S., Cantley L.C., et al. (2015). Adaptive changes in amino acid metabolism permit normal longevity in mice consuming a low-carbohydrate ketogenic diet. Biochimica Biophysica Acta: Molecular Basis of Diseases, 1852(10): 2056–65.
Drincic A.T., Armas L.A.G., Van Diest E.E., Heaney R.P. (2012). Volumetric dilution rather than sequestration best explains the low vitamin D status of obesity. Obesity (Silver Spring), 20(7): 1444–8.
Foster G.D., Wyatt H.R., Hill J.O., McGuckin B.G., Brill C., Mohammed B.S., et al. (2003). A randomized trial of a low-carbohydrate diet for obesity. New England Journal of Medicine, 348(21): 2082–90.
Freire R. (2020). Scientific evidence of diets for weight loss: Different macronutrient composition, intermittent fasting, and popular diets. Nutrition, 69(110549): 110549.
Garbow J.R., Doherty J.M., Schugar R.C., Travers S., Weber M.L., Wentz A.E., et al. (2011). Hepatic steatosis, inflammation, and ER stress in mice maintained long term on a very low-carbohydrate ketogenic diet. American Journal of Physiology: Gastrointestinal and Liver Physiology, 300(6): G956-67.
García O.P., Long K.Z., Rosado J.L. (2009). Impact of micronutrient deficiencies on obesity. Nutrition Reviews, 67(10): 559–72.
Gomez-Arbelaez D., Crujeiras A.B., Castro A.I., Martinez-Olmos M.A., Canton A., Ordoñez-Mayan L., et al. (2018). Resting metabolic rate of obese patients under very low-calorie ketogenic diet. Nutrition and Metabolism (Lond) [Internet], 15(1).
Grandl G., Straub L., Rudigier C., Arnold M., Wueest S., Konrad D., et al. (2018). Short-term feeding of a ketogenic diet induces more severe hepatic insulin resistance than an obesogenic high-fat diet: A short-term ketogenic diet induces hepatic insulin resistance. Journal of Physiology, 596(19): 4597–609.
Heaney R.P., Armas L.A.G., Shary J.R., Bell N.H., Binkley N., Hollis B.W. (2008). 25-Hydroxylation of vitamin D3: relation to circulating vitamin D3 under various input conditions. American Journal of Clinical Nutrition, 87(6): 1738–42.
Hernandez A., Truckenbrod L., Federico Q., Campos K., Moon B., Ferekides N., et al. (2020). Metabolic switching is impaired by aging and facilitated by ketosis independent of glycogen. Aging (Albany NY), 12(9): 7963–84.
Holland A.M., Kephart W.C., Mumford P.W., Mobley C.B., Lowery R.P., Shake J.J., et al. (2016). Effects of a ketogenic diet on adipose tissue, liver, and serum biomarkers in sedentary rats and rats that exercised via resisted voluntary wheel running. American Journal of Physiology: Regulatory Integration and Comparative Physiology, 311(2): R337-51.
James M.J., Gibson R.A., Cleland L.G. (2000). Dietary polyunsaturated fatty acids and inflammatory mediator production. American Journal of Clinical Nutrition, 71(1): 343s–8s.
Johnstone A.M., Horgan G.W., Murison S.D., Bremner D.M., Lobley G.E. (2008). Effects of a high-protein ketogenic diet on hunger, appetite, and weight loss in obese men feeding ad libitum. American Journal of Clinical Nutrition, 87(1): 44–55.
Jonasson L., Guldbrand H., Lundberg A.K., Nystrom F.H. (2014). Advice to follow a low-carbohydrate diet has a favorable impact on low-grade inflammation in type 2 diabetes compared with advice to follow a low-fat diet. Annals of Medicine, 46(3): 182–7.
Jornayvaz F.R., Birkenfeld A.L., Jurczak M.J., Kanda S., Guigni B.A., Jiang D.C., et al. (2011). Hepatic insulin resistance in mice with hepatic overexpression of diacylglycerol acyltransferase 2. Proceedings of National Academy of Science (USA), 108(14): 5748–52.
Kennedy A.R., Pissios P., Otu H., Xue B., Asakura K., Furukawa N., et al. (2007). A high-fat, ketogenic diet induces a unique metabolic state in mice. American Journal of Physiology, Endocrinology, and Metabolism, 292(6): E1724–39.
Kim M., Na W., Sohn C. (2013). Correlation between vitamin D and cardiovascular disease predictors in overweight and obese Koreans. Journal of Clinical Biochemistry and Nutrition, 52(2): 167–71.
Kinzig K.P., Honors M.A., Hargrave S.L. (2010). Insulin sensitivity and glucose tolerance are altered by maintenance on a ketogenic diet. Endocrinology, 151(7): 3105–14.
Lamont B.J., Waters M.F., Andrikopoulos S. (2016). A low-carbohydrate high-fat diet increases weight gain and does not improve glucose tolerance, insulin secretion, or β-cell mass in NZO mice. Nutrition and Diabetes, 6(2): e194–e194.
Lecomte V., Kaakoush N.O., Maloney C.A., Raipuria M., Huinao K.D., Mitchell H.M., et al. (2015). Changes in gut microbiota in rats fed a high-fat diet correlate with obesity-associated metabolic parameters. PLoS One, 10(5): e0126931.
Lee Y.S., Kim J-W., Osborne O., Oh D.Y., Sasik R., Schenk S., et al. (2014). Increased adipocyte O2 consumption triggers HIF-1α, causing inflammation and insulin resistance in obesity. Cell, 157(6): 1339–52.
Lee Y.S., Li P., Huh J.Y., Hwang I.J., Lu M., Kim J.I., et al. (2011). Inflammation is necessary for long-term but not short-term high-fat diet-induced insulin resistance. Diabetes, 60(10): 2474–83.
Leggio M., Lombardi M., Caldarone E., Mazza A., Fusco A. (2018). High body mass index, healthy metabolic profile, and low visceral adipose tissue: The paradox is to call it obesity again. European Journal of Internal Medicine, 52: e15–6.
Maestro B., Campión J., Dávila N., Calle C. (2000). Stimulation by 1,25-dihydroxyvitamin D3 of insulin receptor expression and insulin responsiveness for glucose transport in U-937 human promonocytic cells. Endocrine Journal, 47(4): 383–91.
Makki K., Froguel P., Wolowczuk I. (2013). Adipose tissue in obesity-related inflammation and insulin resistance: cells, cytokines, and chemokines. -139239.
Mazahery H., Stonehouse W., von Hurst P.R. (2015). The effect of monthly 50 000 IU or 100 000 IU vitamin D supplements on vitamin D status in premenopausal Middle Eastern women living in Auckland. European Journal of Clinical Nutrition, 69(3): 367–72.
Meerza D., Naseem I., Ahmed J. (2012). Effect of 1, 25(OH)₂ vitamin D₃ on glucose homeostasis and DNA damage in type 2 diabetic mice. Journal of Diabetes Complications, 26(5): 363–8.
Mitri J., Dawson-Hughes B., Hu F.B., Pittas A.G. (2011). Effects of vitamin D and calcium supplementation on pancreatic β cell function, insulin sensitivity, and glycemia in adults at high risk of diabetes: the Calcium and Vitamin D for Diabetes Mellitus (CaDDM) randomized controlled trial. American Journal of Clinical Nutrition, 94(2): 486–94.
Mitri J., Pittas A.G. (2014). Vitamin D and diabetes. Endocrinology and Metabolism: Clinics of North America, 43(1): 205–32.
Moreno B., Crujeiras A.B., Bellido D., Sajoux I., Casanueva F.F. (2016). Obesity treatment by very low-calorie-ketogenic diet at two years: reduction in visceral fat and on the burden of disease. Endocrine, 54(3): 681–90.
Murata Y., Nishio K., Mochiyama T., Konishi M., Shimada M., Ohta H., et al. (2013). Fgf21 impairs adipocyte insulin sensitivity in mice fed a low-carbohydrate, high-fat ketogenic diet. PLoS One, 8(7): e69330.
Muscogiuri G., Sorice G.P., Ajjan R., Mezza T., Pilz S., Prioletta A., et al. (2012). Can vitamin D deficiency cause diabetes and cardiovascular diseases? Present evidence and future perspectives. Nutrition, Metabolism, and cardiovascular diseases, 22(2): 81–7.
National Research Council, Division on Earth and Life Studies, Institute for Laboratory Animal Research, Committee for the Update of the Guide for the Care and Use of Laboratory Animals. (2011). Guide for the care and use of Laboratory Animals: Eighth Edition. Washington, D.C., DC: National Academies Press.
Nigro E., Scudiero O., Sarnataro D., Mazzarella G., Sofia M., Bianco A., et al. (2013). Adiponectin affects lung epithelial A549 cell viability counteracting TNFa and IL-1ß toxicity through AdipoR1. International Journal of Biochemistry and Cell Biology, 45(6): 1145–53.
Niramitmahapanya S., Harris S.S., Dawson-Hughes B. (2011). Type of dietary fat is associated with the 25-hydroxyvitamin D3 increment in response to vitamin D supplementation. Journal of Clinical Endocrinology & Metabolism, 96 (10): 3170–3174.
Pereira-Santos M., Costa P.R.F., Assis A.M.O., Santos C.A.S.T., Santos D.B. (2015). Obesity and vitamin D deficiency: A systematic review and meta-analysis: Obesity and vitamin D. Obesity Reviews, 16(4): 341–9.
Pérez-Matute P., Pérez-Echarri N., Martínez J.A., Marti A., Moreno-Aliaga M.J. (2007). Eicosapentaenoic acid actions on adiposity and insulin resistance in control and high-fat-fed rats: role of apoptosis, adiponectin and tumour necrosis factor-alpha. British Journal of Nutrition, 97(2): 389–98.
Pittas A.G., Harris S.S., Eliades M., Stark P., Dawson-Hughes B. (2009). Association between serum osteocalcin and markers of metabolic phenotype. Journal of Clinical Endocrinology and Metabolism, 94(3): 827–32.
Rebello C., Greenway F.L., Dhurandhar N.V. (2014). Functional foods to promote weight loss and satiety. Current Opinions in Clinical Nutrition and Metabolic Care, 17(6): 596–604.
Reeves P.G. (1997). Components of the AIN-93 diets as improvements in the AIN-76A diet. Journal of Nutrition, 127(5): 838S-841S.
Rosenbaum M., Hall K.D., Guo J., Ravussin E., Mayer L.S., Reitman M.L., et al. (2019). Glucose and lipid homeostasis and inflammation in humans following an isocaloric ketogenic diet. Obesity (Silver Spring), 27(6): 971–81.
Sampath A., Kossoff E.H., Furth S.L., Pyzik P.L., Vining E.P.G. (2007). Kidney stones and the ketogenic diet: Risk factors and prevention. Journal of Childhood Neurology, 22(4): 375–8.
Sentinelli F., Bertoccini L., Barchetta I., Capoccia D., Incani M., Pani M.G., et al. (2016). The vitamin D receptor (VDR) gene rs11568820 variant is associated with type 2 diabetes and impaired insulin secretion in Italian adult subjects and associated with increased cardio-metabolic risk in children. Nutrition, Metabolism, and cardiovascular diseases, 26(5): 407–13.
Sergeev I.N. (2016). 1,25-dihydroxyvitamin D3 and type 2 diabetes: Ca2+-dependent molecular mechanisms and the role of vitamin D status. Hormones, Molecular Biology and Clinical Investigation, 26(1): 61–5.
Song X., Kestin M., Schwarz Y., Yang P., Hu X., Lampe J.W., et al. (2016). A low-fat high-carbohydrate diet reduces plasma total adiponectin concentrations compared to a moderate-fat diet with no impact on biomarkers of systemic inflammation in a randomized controlled feeding study. European Journal of Nutrition, 55(1): 237–46.
Song Y., Wang L., Pittas A.G., Del Gobbo L.C., Zhang C., Manson J.E., et al. (2013). Blood 25-hydroxy vitamin D levels and incident type 2 diabetes: a meta-analysis of prospective studies. Diabetes Care, 36(5): 1422–8.
Tiosano D., Wildbaum G., Gepstein V., Verbitsky O., Weisman Y., Karin N., (2013). et al. The role of vitamin D receptor in innate and adaptive immunity: a study in hereditary vitamin D-resistant rickets patients. Journal of Clinical Endocrinology and Metabolism, 98(4): 1685–93.
Tremmel M., Gerdtham U-G., Nilsson P.M., Saha S. (2017). Economic burden of obesity: A systematic literature review. International Journal of Environmental Research and Public Health [Internet], 14(4).
Trigueros L., Peña S., Ugidos A.V., Sayas-Barberá E., Pérez-Álvarez J.A., Sendra E. (2013). Food ingredients as anti-obesity agents: A review. Critical Review of Food Science and Nutrition, 53(9): 929–42.
Wadden T.A., Webb V.L., Moran C.H., Bailer B.A. (2012). Lifestyle modification for obesity: new developments in diet, physical activity, and behavior therapy. Circulation, 125(9): 1157–70.
Wareham N.J., Phillips D.I., Byrne C.D., Hales C.N. (1995). The 30-minute insulin incremental response in an oral glucose tolerance test as a measure of insulin secretion. Diabetes Medicine, 12(10): 931.
Wei M.Y., Garland C.F., Gorham E.D., Mohr S.B., Giovannucci E. (2008). Vitamin D and prevention of colorectal adenoma: A meta-analysis. Cancer Epidemiological Biomarkers Preview, 17(11): 2958–69.
Weickert M.O., Roden M., Isken F., Hoffmann D., Nowotny P., Osterhoff M., et al. (2011). Effects of supplemented isoenergetic diets differing in cereal fiber and protein content on insulin sensitivity in overweight humans. American Journal of Clinical Nutrition, 94(2): 459–71.
Westman E.C., Feinman R.D., Mavropoulos J.C., Vernon M.C., Volek J.S., Wortman J.A., et al. (2007). Low-carbohydrate nutrition and metabolism. American Journal of Clinical Nutrition, 86(2): 276–84.
Wimalawansa S.J. (2018). Associations of vitamin D with insulin resistance, obesity, type 2 diabetes, and metabolic syndrome. Journal of Steroid Biochemistry and Molecular Biology, 175: 177–89.
Withrow C.D. (1980). The ketogenic diet: mechanism of anticonvulsant action. Advanced Neurology, 27: 635–42.
Wortsman J., Matsuoka L.Y., Chen T.C., Lu Z., Holick M.F. (2000). Decreased bioavailability of vitamin D in obesity. American Journal of Clinical Nutrition, 72(3): 690–3.
Yan Y., Jiang W., Spinetti T., Tardivel A., Castillo R., Bourquin C., et al. (2013). Omega-3 fatty acids prevent inflammation and metabolic disorder through inhibition of NLRP3 inflammasome activation. Immunity, 38(6): 1154–63.
Yin Y. Yu Z., Xia M., Luo X., Lu X., Ling W. (2012). Vitamin D attenuates high fat diet-induced hepatic steatosis in rats by modulating lipid metabolism: Vitamin D attenuates high fat diet-induced hepatic steatosis in rats. European Journal of Clinical Investigation, 42(11): 1189–96.
Zhao L-J., Zhou Y., Bu F., Travers-Gustafson D., Ye A., Xu X., et al. (2012). Factors predicting vitamin D response variation in non-Hispanic white postmenopausal women. Journal of Clinical Endocrinology and Metabolism, 97(8): 2699–705.
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2021 © 2021 DSR Publishers/The University of Jordan. All Rights Reserved.
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
