Abstract

Obesity is associated with multiple comorbidities such as cardiovascular disease, type 2 diabetes, and cancer ultimately resulting in increased mortality. Because of this, many individuals attempt to lose weight, but weight loss is often not maintained leading to the practice of weight cycling. Since human studies evaluating the effects of weight cycling on mortality are in disagreement with one another, and no animal studies had been performed on this topic, our laboratory conducted the first animal study to determine if stable obesity or weight cycling is more detrimental to lifespan. Our results showed that weight cycled mice significantly outlived their obese counterparts suggesting that weight cycling is healthier than remaining obese. However, weight cycling is a complex behavior with an infinite number of parameters. Thus, in the current study, we sought to expand our weight cycling model by investigating the effect of cycle duration on lifespan. Specifically, we evaluated the effect of doubling our previous four week cycle to eight weeks and measured the effect of this change on lifespan. One hundred male C57BL/6J mice were placed on one of four lifelong diets: a high fat diet (HF; n=30), a low fat diet (LF; n=30), a cycled diet alternating between 4 weeks on a low fat diet followed by 4 weeks on a high fat diet (4wk; n=20) or a cycled diet alternating between 8 weeks on a low fat diet and 8 weeks on a high fat diet (8wk; n=20). Caloric consumption, body weight, body composition, blood glucose, and lifespan were assessed. As expected caloric consumption, body weight, fat mass, and blood glucose levels were significantly higher in HF fed mice than LF controls and these values fluctuated significantly between cycles in weight cycled mice (increasing while on the HF diet and decreasing while on the LF diet). The mean lifespans were the following for each group: LF: 896.7 days, HF: 638.7 days, 4wk: 724.9 days, and 8wk: 749.7 days. Log-rank (Mantel-cox) analyses reveal that HF fed mice were significantly shorter lived than the other three groups while LF fed mice were significantly longer lived than the other three groups. Both weight cycled groups were shorter lived than the LF fed group and longer lived than the HF fed group. Finally, lifespan did not differ between 4wk and 8wk weight cycled groups. In conclusion, these findings demonstrate that altering cycle duration in weight cycled mice from 4 to 8 weeks does not alter lifespan. Importantly, both 4wk and 8wk weight cycled groups outlived stable obese controls suggesting that lifelong weight cycling is not more deleterious to health than remaining obese.

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