Very low-carbohydrate, high-fat, weight reduction diet decreases hepatic gene response to glucose in obese rats
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RESEARCH
Open Access
Very low-carbohydrate, high-fat, weight reduction diet decreases hepatic gene response to glucose in obese rats Kathleen V. Axen*, Marianna A. Harper, Yu Fu Kuo and Kenneth Axen
Abstract Background: Very low carbohydrate (VLC) diets are used to promote weight loss and improve insulin resistance (IR) in obesity. Since the high fat content of VLC diets may predispose to hepatic steatosis and hepatic insulin resistance, we investigated the effect of a VLC weight-reduction diet on measures of hepatic and whole body insulin resistance in obese rats. Methods: In Phase 1, adult male Sprague-Dawley rats were made obese by ad libitum consumption of a high-fat (HF1, 60% of energy) diet; control rats ate a lower-fat (LF, 15%) diet for 10 weeks. In Phase 2, obese rats were fed energy-restricted amounts of a VLC (5%C, 65%F), LC (19%C, 55%F) or HC (55%C, 15%F) diet for 8 weeks while HF2 rats continued the HF diet ad libitum. In Phase 3, VLC rats were switched to the HC diet for 1 week. At the end of each phase, measurements of body composition and metabolic parameters were obtained. Hepatic insulin resistance was assessed by comparing expression of insulin-regulated genes following an oral glucose load,that increased plasma insulin levels, with the expression observed in the feed-deprived state. Results: At the end of Phase 1, body weight, percent body fat, and hepatic lipid levels were greater in HF1 than LF rats (p < 0.05). At the end of Phase 2, percent body fat and intramuscular triglyceride decreased in LC and HC (p < 0.05), but not VLC rats, despite similar weight loss. VLC and HF2 rats had higher HOMA-IR and higher insulin at similar glucose levels following an ip glucose load than HC rats (p < 0.05). HC, but not VLC or HF2 rats, showed changes in Srebf1, Scd1, and Cpt1a expression (p < 0.05) in response to an oral glucose load. At the end of Phase 3, switching from the VLC to the HC diet mitigated differences in hepatic gene expression. Conclusion: When compared with a high-carbohydrate, low-fat diet that produced similar weight loss, a commonly used VLC diet failed to improve whole body insulin resistance; it also reduced insulin’s effect on hepatic gene expression, which may reflect the development of hepatic insulin resistance. Keywords: Very low-carbohydrate diet, Weight loss, Insulin resistance, Lipogenesis, Gene expression, Obesity
Background Very low carbohydrate (VLC, < 10% of energy) diets that are used to reduce body weight and improve glycemic control and insulin sensitivity in obese individuals [1, 2] generally provide > 50% of energy as fat [3–5]. High levels of dietary fat are implicated in the development of hepatic steatosis [6–8] which is prevalent in the obese population and is associated with hepatic insulin resistance and development of Type 2 diabetes mellitus [9]. * Correspondence: [email protected] Department of Health and Nutrition Sciences, Brooklyn College, City University of New York, New York, USA
Since obese individuals who are at risk for Type 2 diabetes melli
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