Poudyal H, Panchal SK, Ward LC, Waanders J, Brown L. Chronic high-carbohydrate, high-fat feeding in rats induces reversible metabolic, cardiovascular, and liver changes. Am J Physiol Endocrinol Metab 302: E1472-E1482, 2012. First published March 20, 2012 doi:10.1152/ajpendo.00102.2012.-Age-related physiological changes develop at the same time as the increase in metabolic syndrome in humans after young adulthood. There is a paucity of data in models mimicking chronic diet-induced changes in human middle age and interventions to reverse these changes. This study measured the changes during chronic consumption of a high-carbohydrate (as cornstarch), low-fat (C) diet and a high-carbohydrate (as fructose and sucrose), high-fat (H) diet in rats for 32 wk. C diet feeding induced changes without metabolic syndrome, such as disproportionate increases in total body lean and fat mass, reduced bone mineral content, cardiovascular remodeling with increased systolic blood pressure, left ventricular and arterial stiffness, and increased plasma markers of liver injury. H diet feeding induced visceral adiposity with reduced lean mass, increased lipid infiltration in the skeletal muscle, impaired glucose and insulin tolerance, cardiovascular remodeling, hepatic steatosis, and increased infiltration of inflammatory cells in the heart and the liver. Chia seed supplementation for 24 wk attenuated most structural and functional modifications induced by age or H diet, including increased whole body lean mass and lipid redistribution from the abdominal area, and normalized the chronic low-grade inflammation induced by H diet feeding; these effects may be mediated by increased metabolism of anti-inflammatory n-3 fatty acids from chia seed. These results suggest that chronic H diet feeding for 32 wk mimics the diet-induced cardiovascular and metabolic changes in middle age and that chia seed may serve as an alternative dietary strategy in the management of these changes. obesity; chia seed; omega-3 fatty acids; metabolic syndrome METABOLIC SYNDROME is defined as a cluster of risk factors, including type 2 diabetes mellitus, hypertension, dyslipidemia, and central obesity, leading to cardiovascular diseases (3). The worldwide pandemic of metabolic syndrome and, particularly, central obesity, has been attributed to increased consumption of lipogenic sugars, such as fructose, together with saturated fats (1, 37). The Western diet, characterized by excessive intake of saturated and trans fatty acids and a low n-3-to-n-6 polyunsaturated fatty acid (PUFA) ratio, has been associated with chronic diseases such as metabolic syndrome, renal diseases, and arthritis (2,12,24,36).Early onset of obesity is a key predictor of type 2 diabetes, dyslipidemia, hypertension, and obesity in young adulthood and middle age (9,13,19,20). Childhood or adolescent obesity is a direct cause of cardiovascular disease in young, middleaged, and elderly populations and increased all-cause mortality (25). The progression from childhood through middle age to old age is...