Impairment of fat oxidation under high- vs. low-glycemic index diet occurs before the development of an obese phenotype

Abstract

Exposure to high vs. low glycemic index (GI) diets increases fat mass and insulin resistance in obesity-prone C57BL/6J mice. However, the longer-term effects and potentially involved mechanisms are largely unknown. We exposed four groups of male C57BL/6J mice (n ϭ 10 per group) to long-term (20 wk) or short-term (6 wk) isoenergetic and macronutrient matched diets only differing in starch type and as such GI. Body composition, liver fat, molecular factors of lipid metabolism, and markers of insulin sensitivity and metabolic flexibility were investigated in all four groups of mice. Mice fed the high GI diet showed a rapid-onset (from week 5) marked increase in body fat mass and liver fat, a gene expression profile in liver consistent with elevated lipogenesis, and, after long-term exposure, significantly reduced glucose clearance following a glucose load. The long-term high-GI diet also led to a delayed switch to both carbohydrate and fat oxidation in the postprandial state, indicating reduced metabolic flexibility. In contrast, no difference in carbohydrate oxidation was observed after short-term high-vs. low-GI exposure. However, fatty acid oxidation was significantly blunted as early as 3 wk after beginning of the high-GI intervention, at a time where most measured phenotypic markers including body fat mass were comparable between groups. Thus long-term high-GI feeding resulted in an obese, insulin-resistant, and metabolically inflexible phenotype in obesity-prone C57BL/6J mice. Early onset and significantly impaired fatty acid oxidation preceded these changes, thereby indicating a potentially causal involvement. glycemic index; fat metabolism; body fat; insulin resistance; liver fat; metabolic flexibility; insulin resistance EXPOSURE TO HIGH VS. LOW glycemic index (GI) diets unfavorably affects fat mass and markers of insulin resistance in rodent models (1, 12, 15-17, 21, 23). Metabolic flexibility that can be defined as the capacity to adapt fuel oxidation to fuel availability (3, 7, 13) could also be changed by a high-GI diet, although no consensus exists as to whether diets varying in GI directly affect substrate oxidation or energy expenditure (4, 21). Alternatively, changes in substrate oxidation might be mainly a consequence of high-vs. low-GI diet-induced differences, e.g., in body weight, body fat distribution, or insulin resistance. Therefore, elucidating whether changes in substrate oxidation follow or precede an obese phenotype in high-GI-fed animals could be helpful for the understanding of potentially involved mechanisms.Most of the previous studies investigating effects of highvs. low-GI diets on metabolic markers were relatively short term (1,12,15,16,23), lasting between 3 and up to 13 wk. We are aware of only two previous longer-term studies, both of which reported unfavorable effects of high-vs. low-GI diets on body fat distribution and metabolic markers in rodents (17, 21). However, the first study (18 wk) investigated partial pancreatectomized male Sprague-Dawley rats, which is an animal mo...

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