Adipose tissue metabolism and inflammation are differently affected by weight loss in obese mice due to either a high-fat diet restriction or change to a low-fat diet

Abstract

Restriction of a high-fat diet (HFD) and a change to a low-fat diet (LFD) are two interventions that were shown to promote weight loss and improve parameters of metabolic health in obesity. Examination of the biochemical and molecular responses of white adipose tissue (WAT) to these interventions has not been performed so far. Here, male C57BL/6JOlaHsd mice, harboring an intact nicotinamide nucleotide transhydrogenase gene, were fed a purified 40 energy% HFD for 14 weeks to induce obesity. Afterward, mice were divided into three dietary groups: HFD (maintained on HFD), LFD (changed to LFD with identical ingredients), and HFD-CR (restricted to 70 % of the HFD). The effects of the interventions were examined after 5 weeks. Beneficial effects were seen for both HFD-CR and LFD (compared to HFD) regarding physiological parameters (body weight and fat mass) and metabolic parameters, including circulating insulin and leptin levels. Macrophage infiltration in WAT was reduced by both interventions, although more effectively by HFD-CR. Strikingly, molecular parameters in WAT differed between HFD-CR and LFD, with increased activation of mitochondrial carbohydrate and fat metabolism in HFD-CR mice. Our results confirm that restriction of the amount of dietary intake and reduction in the dietary energy content are both effective in inducing weight loss. The larger decrease in WAT inflammation and increase in mitochondrial carbohydrate metabolism may be due to a larger degree of energy restriction in HFD-CR, but could also be due to superior effectiveness of dietary restriction in weight loss strategies.

Removal of a high-fat diet, but not voluntary exercise, reverses obesity and diabetic-like symptoms in male C57BL/6J mice

“…These results indicate that it is not just the increase in calories consumed that can lead to obesity in these DIO mice but food composition as well. Interestingly, both food switch (i.e., ad libitum feeding of regular chow) 3,19 and caloric restriction of a high-fat diet 19,25 produce significant improvements in obesity and insulin resistance in rodent models. While there are numerous parallel results between calorie restriction and switching to a low-fat diet, one remaining question is whether leptin levels are similarly affected by these two treatments.…”

“…A study which investigated both restricted high-fat diet and switch to regular chow showed mice having similarly reduced levels of leptin compared to high-fat diet consuming mice. 19 Additional studies may be needed to fully determine whether it is the reductions in caloric intake or in fat content that most effectively reduce leptin levels in obese individuals.…”

“…Both voluntary wheel-running 15,16 and forced exercise 17,18 are effective in improving health and reducing obesity in rodents fed a high-fat diet; however, these animals were still overweight and exhibited more unhealthy characteristics than sedentary animals on low-fat diets (low-fat diet). Switching high-fat diet fed rodents to a low-fat diet can promote weight loss, 19 but there is some evidence showing that these animals may not fully recover from the obesogenic effects of the high-fat diet and remain heavier than their low-fat diet controls even after the high-fat diet is removed. 20 However, few studies in the animal literature have investigated the combined effects of exercise and consumption of an improved diet on physiological characteristics or if the obesity and type-2 diabetic phenotype can be improved after a shorter timeframe of healthy behavior (weeks as opposed to months).…”

Caloric restriction improves diabetes-induced cognitive deficits by attenuating neurogranin-associated calcium signaling in high-fat diet-fed mice

“…The total caloric intake of CR diet was comparable to that of ND (p ¼ 0.23) and the total caloric intake of HFDþCR was restricted to $70% of the HFD. 29,30 Mice were weighed monthly and before sacrifice.…”

Comparison of two Kampo medicines in a diet‐induced mouse obesity model

“…In this study, we used one of the major pre‐clinical animal models for studying obesity, which is the high‐fat diet‐induced obesity (DIO) model, to conduct a comparative study of the therapeutic efficacy of BOT and BTS in obesity. The DIO model shares many of the same phenotypes as in human disease, including visceral adiposity, insulin resistance, hyperinsulinemia, hyperleptinemia, and leptin resistance . Although neither BOT nor BTS had any significant impact on body composition in the DIO mice, BOT and BTS treatment altered the serum level of leptin and insulin in the DIO mice.…”