Consumption of a high-carbohydrate diet has a critical role in the induction of weight gain and obesity-related pathologies. This study tested the hypothesis that a carbohydrate-rich diet induces ...weight gain, ectopic fat deposition, associated metabolic risks and development of non-alcoholic fatty liver disease (NAFLD), which are partially reversible following carbohydrate reduction. Sprague Dawley (SD) rats were fed a carbohydrate-enriched cafeteria diet (CAF) or normal chow (NC) ad libitum for 16-18 weeks. In the reversible group (REV), the CAF was replaced with NC for a further 3 weeks (18-21 weeks). Animals fed the CAF diet showed significantly increased body weight compared to those fed NC, accompanied by abnormal changes in their systemic insulin and triglycerides, elevation of hepatic triglyceride and hepatic steatosis. In the REV group, when the CAF diet was stopped, a modest, non-significant weight loss was associated with improvement in systemic insulin and appearance of the liver, with lower gross fatty deposits and hepatic triglyceride. In conclusion, a carbohydrate-enriched diet led to many features of metabolic syndrome, including hyperinsulinemia, while a dietary reduction in this macronutrient, even for a short period, was able to restore normoinsulinemia, and reversed some of the obesity-related hepatic abnormalities, without significant weight loss.
Global prevalence of obesity is increasing enormously and has more than doubled since 1980 as reported by World Health Organization (WHO). Currently obesity and overweight affect more than a third of ...the world's population, with obesity, as a disease, considered a global epidemic. Major causative factors for this epidemic are easy access to high energy-dense food, and sedentary lifestyle. Increasing body weight, associated with high fat mass, is a risk factor for metabolic syndrome (MS) affecting the function of several organs. Lifestyle intervention is a successful treatment in reversing obesity-related comorbidities. How obesity leads to the development of cardiometabolic risk and how these, in turn may be reversed with lifestyle intervention is the focus of much recent research. Therefore, the current study tested the hypothesis that high carbohydrate diet increases ectopic fat deposition, cardio-metabolic risk, and development of non-alcoholic fatty liver disease (NAFLD), which are wholly or partially reversible by diet-induced weight loss. Male Sprague Dawley (SD) rats aged 8-9 weeks, were assigned into three groups: NC group fed with Normal chow (NC) and access to normal water ad libitum, CAF group fed with both diets; cafeteria style diet (CAF) and NC with 5% sugar water ad libitum for a period of 16 weeks, and, reversibility group (REV) fed with CAF diet and NC ad libitum to induce obesity and then switched to NC for three weeks duration to induce weight loss. The CAF diet significantly increased body weight, directly related to greater consumption of this diet, compared to NC. This was associated with abnormalities in the metabolic parameters. Data from the vascular studies revealed that acetylcholine (Ach) mediated relaxation was significantly compromised following CAF feeding, suggesting endothelial dysfunction. In addition, CAF feeding induced hepatic fat accumulation and the development of grade 3 hepatic steatosis. At the transcriptome level the CAF diet stimulated de novo lipogenesis mediated by the over-expression of sterol regulatory element binding transcription factor 1 (SREBF1) and the dysregulation of lipogenic genes. In the REV group, rats showed a trend towards weight loss, though it did not reach statistical significance (approximately 6% in three weeks). However, this decrease in weight was enough to improve metabolic parameters, to be more reflective of normal levels. Vascular studies revealed that endothelial dysfunction was not reversed by CAF withdrawal. However, great improvement was observed in hepatic steatosis. Transcriptomic analysis showed improvement in hepatic steatosis, mediated by increase in expression of genes related to fatty acid (FA) oxidation, lipid export and hepatic tissue repair. In conclusion, the study successfully developed a diet-induced obese rat model that mimics human obesity following consumption of the regional diet (Arabian Peninsula) and demonstrated the expected metabolic changes. Further, this deterioration in metabolic function may be corrected by diet-induced weight loss. Endothelial dysfunction appeared less amenable to reversibility by short-term weight loss. However, fat accumulation around the liver decreased with slight weight loss, suggesting that lifestyle modification, especially diet is an effective strategy to address hepatic steatosis.
