Abstract
BackgroundVery 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.MethodsIn 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.ResultsAt 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.ConclusionWhen 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.
Highlights
Very low carbohydrate (VLC) diets are used to promote weight loss and improve insulin resistance (IR) in obesity
Ketosis diets lowered basal blood glucose and insulin levels in normal mice [27] and murine models of type 2 diabetes [23, 28], these diets produced glucose intolerance, as well as hepatic [27] and whole body insulin resistance [29]. These results show that VLC diets with a low protein content can produce hepatic steatosis and hepatic insulin resistance
Research design In order to compare the effects of weight reduction by a VLC diet with that of a high-carbohydrate, lower-fat diet (HC), we first made rats obese in Phase 1 by ad libitum consumption of a high-fat diet for 10 weeks (HF1); rats consuming a lower-fat diet ad libitum served as a normal control group (LF, Fig. 1)
Summary
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. Previous studies from our laboratory in obese rats showed that an energy-restricted VLC diet produced less reduction in visceral fat, and hepatic and intramuscular lipid levels, and less improvement in glucose tolerance than an isocaloric high-carbohydrate, low-fat diet that yielded similar weight loss [17, 18]. The correlation between hepatic lipid concentration and glucose intolerance in that study [18] provided the impetus for the present investigation of the effects of a VLC weight-reduction diet on hepatic and whole body insulin resistance
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