The effects of weight cycling on lifespan in male C57BL/6J mice

Abstract

ObjectiveWith the increasing rates of obesity, many people diet in attempts to lose weight. Since weight loss is seldom maintained in a single effort, weight cycling is a common occurrence. Unfortunately, reports from clinical studies that have attempted to determine the effect of weight cycling on mortality are in disagreement, and to date, no controlled animal study has been performed to assess the impact of weight cycling on longevity. Therefore, our objective was to determine whether weight cycling altered lifespan in mice that experienced repeated weight gain and weight loss throughout their lives.MethodsMale C57BL/6J mice were placed on one of three lifelong diets: a low fat (LF) diet, a high fat (HF) diet, or a cycled diet in which the mice alternated between 4 weeks on the LF diet and 4 weeks on the HF diet. Body weight, body composition, several blood parameters and lifespan were assessed.ResultsCycling between the HF and LF diet resulted in large fluctuations in body weight and fat mass. These gains and losses corresponded to significant increases and decreases, respectively, in leptin, resistin, GIP, IGF-1, glucose, insulin, and glucose tolerance. Surprisingly, weight cycled mice had no significant difference in lifespan (801±45 days) as compared to LF fed controls (828±74 days), despite being overweight and eating a HF diet for half of their lives. In contrast, the HF fed group experienced a significant decrease in lifespan (544±73days) compared to LF fed controls and cycled mice.ConclusionsThis is the first controlled mouse study to demonstrate the effect of lifelong weight cycling on longevity. The act of repeatedly gaining and losing weight, in itself, did not decrease lifespan and was more beneficial than remaining obese.

hNAG-1 increases lifespan by regulating energy metabolism and insulin/IGF-1/mTOR signaling

“…On HFD, the median lifespan of hNAG-1 mice was 22.4 weeks (23.6%) and 33.6 weeks (43.6%) longer than WT littermates, respectively for lines 1377 and 1398 (log rank χ 2 = 13.0, 1 d.f., p<0.001 for line 1377; log rank χ 2 = 28.9, 1 d.f., p<0.001 for line 1398, Table 1). Consistent with previous findings that HFD could shorten lifespan[8, 9], survival of line 1398 WT mice in the HFD group was significantly lower than the LFD group (median was 24 weeks lower, log rank χ 2 = 11.2, 1 d.f., p < 0.001). However, there were no significant differences in lifespan between HFD and LFD in either WT or hNAG-1 transgenic mice in line 1377.…”

“…In early life, rodents fed a caloric restriction diet have lower IGF-1 levels than rodents fed a normal chow diet, and many rodent genetic models with a prolonged lifespan have lower levels of serum IGF-1 or IIS signaling compared to control groups [5-7]. In contrast, HFD promotes mortality and decreases lifespan in laboratory animals [8, 9]. …”

Weight cycling promotes fat gain and altered clock gene expression in adipose tissue in C57BL/6J mice

“…It may also be worth noting that the increased adiposity after weight cycling did not further deteriorate insulin resistance. Interestingly, a relative protection against obesity-related metabolic complications due to feeding pattern was indicated by recent studies showing beneficial effects of time-restricted feeding on metabolic disease (20) and of weight cycling on longevity compared with a steady state of obesity (38). Of note, the mice on time-restricted feeding showed altered expression of clock genes in the liver.…”

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“…It is evident that remaining at a stable weight and on a healthy diet provides the best outcomes for health, however research reveals that weight cycling does not decrease lifespan and is more beneficial to health than being obese or overweight [6,8,11,12]. Therefore the maintenance stage for this patient needs to be a continuation of behavioral change, not a termination of behavioral change.…”

“…This can be viewed as TTM cycling or, more specifically for these patients, weight cycling. The patient that presents as a weight cycler repeatedly progresses through the stages of the TTM therefore requiring ongoing weight management and behavioral health counseling and treatment [5,11]. When utilizing the Transtheoretical Model for weight loss and weight loss maintenance therapists and patients need to focus on a continuation of behavioral change, not a termination of behavioral change.…”