Ketogenic diet‐induced weight loss occurs independent of housing temperature and is followed by hyperphagia and weight regain after cessation in mice

Abstract

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Changes in Macronutrients during Dieting Lead to Weight Cycling and Metabolic Complications in Mouse Model

“…Notably, numerous long-term studies on low-carbohydrate, high-fat diets (LCHFD) have demonstrated weight loss despite the high caloric consumption [ 27 , 28 ]. However, our study reveals that transitioning from an LCHFD to a Western diet (WD) under isocaloric conditions also results in considerable weight regain, suggesting that the trigger for weight cycling lies in the return to a WD [ 29 ]. The impact of carbohydrates on weight gain has previously been suggested to be a central element in the development of obesity.…”

“…We hypothesize that fluctuations in insulin levels in response to shifts in macronutrient intake may contribute to the development of weight cycling, thus explaining the weight regain phenomenon. Several studies have shown that LCHFD consumption significantly decreases insulin levels while WD consumption is associated with obesity development and high insulin levels [ 27 , 29 , 40 ]. Therefore, the return of a high-fat, high-sugar WD after LCHFD-induced weight loss could lead to hyperinsulinemia and promote weight regain.…”

“…These results may suggest that a reduction in FGF21 can participate in the progression of obesity in both WD and I-WD mice. The decrease in FGF21 was unexpected in the I-WD group, as an LCHFD usually strongly increases the FGF21 gene and protein expression [ 28 , 29 ]. These findings imply that weight cycling could lead to FGF21 disturbance and promote the development of metabolic complications.…”

“…In the face of the inefficiency of caloric restriction in weight loss maintenance, a hypercaloric diet, based on changes in macronutrient distribution without caloric restriction, offers a promising strategy for preventing obesity complications. The hypercaloric low-carbohydrate, high-fat diet (LCHFD) reduces weight gain and insulin levels and improves glucose tolerance in diet-induced obese mice [ 27 , 28 , 29 ]. In clinical trials, an LCHFD induced weight loss and decreased blood glucose levels, steatosis, and aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels in patients with obesity [ 30 , 31 , 32 , 33 , 34 ].…”

Still Excited, but Less Aroused—The Effects of Nutritional Ketosis on Epinephrine Response and Hypothalamic Orexin Neuron Activation Following Recurrent Hypoglycemia in Diabetic Rats

“…Ketogenic diet consumption leads to weight loss in overweight and obese humans [ 37 ] and reduced weight gain in normal weight rodents [ 38 , 39 ], largely due to decreased food intake [ 40 ]. Consistent with the literature, our study found that both non-diabetic and STZ-diabetic keto-fed rats had lower bodyweights than the respective chow control animals.…”