Metabolic dysfunction following weight cycling in male mice

Abstract

BackgroundCombatting over-weight or obesity can lead to large fluctuations in an individual’s body weight, often referred to as weight cycling or “yo-yo” dieting. Current evidence regarding the potentially damaging effects of these changes is conflicting.MethodsHere, we assess the metabolic effects of weight cycling in a murine model, comprising three dietary switches to normal or high fat diets at 6 week intervals; male C57BL/6 mice were fed either a control (C) or high fat (F) diet for 6 weeks (n=140/group). C and F groups were then either maintained on their initial diet (CC and FF respectively) or switched to a high fat (CF) or control (FC) diet (n=35/group). For the final 6 week interval, CC and CF groups were returned to the control diet (CCC and CFC groups) while FC and FF groups were placed on a high fat diet (FCF and FFF) (n=28/group).ResultsFor the majority of metabolic outcomes changes aligned with dietary switches; however assessment of neuropeptides and receptors involved in appetite regulation and reward signalling pathways reveal variable patterns of expression. Furthermore, we demonstrate that multiple cycling events leads to a significant increase in internal fat deposition, even when compared to animals maintained on a high fat diet (Internal Fat: FCF: 7.4 ± 0.2g vs. FFF: 5.6 ± 0.2g; p<0.01).ConclusionsIncreased internal adipose tissue is strongly linked to the development of metabolic syndrome associated conditions such as type 2 diabetes, cardiovascular disease and hypertension. While further work will be required to elucidate the mechanisms underlying the neuronal control of energy homeostasis, these studies provide a causative link between weight cycling and adverse health.

Lmo4‐resistin signaling contributes to adipose tissue‐liver crosstalk upon weight cycling

“…36,37 Moreover, multiple clinical and animal studies, including the present study ( Figures 1G and 2D), indicated that healthy and unhealthy diet switch induced weight cycling ultimately increases body fat gain, specifically in the visceral adipose tissue. 4,38 Notably, the present study demonstrated increased A, qPCR results of Il-6 and Il-8 in primary hepatocytes stimulated with media from indicated 3T3-L1 cells. B, Representative western blots of p-STAT3 and STAT3 (left) with quantification result of p-STAT3/STAT3 ratio (right) in primary hepatocytes stimulated with media from indicated 3T3-L1 cells.…”

Body Weight Cycling with Identical Diet Composition Does Not Affect Energy Balance and Has No Adverse Effect on Metabolic Health Parameters

“…In these studies, EE was not measured. Other studies either did not analyze BW regain after BW cycling [ 11 ], or did not allow animals to regain BW in their natural way towards a new equilibrium [ 8 , 12 , 22 , 23 ], or did not include one-BW cycle control groups [ 6 , 8 , 9 , 24 ], or used very short duration cycles and/or total food deprivation [ 15 , 16 , 25 ], or analyzed only one cycle [ 14 ]. In the three studies with which we could compare, BW gain over the total study period was reduced after BW cycling [ 17 , 20 , 21 ].…”

“…In the only other BW cycling study performed in mice (of unknown gender), comparable food efficiencies between three cycling groups were observed [ 22 ]. Other BW cycling studies, using dietary changes to induce cycles showed no or increased food efficiency [ 5 , 7 , 14 ] or did not measure this parameter [ 6 , 8 , 10 , 11 , 22 , 26 , 27 ]. Based on these data, it seems that BW cycling without dietary changes does not lead to increased food efficiency.…”

“…In summary, negative effects of BW cycling are firmly embedded in public opinion, but the existing published data on humans and animals do not allow for firm conclusions about the (metabolic) health consequences of BW cycling. This is at least partly due to the large variety in experimental approaches; e.g., BW cycles are often induced by a change between diets [ 10 , 11 , 12 , 13 , 14 ], and by the use of non-purified diets (all studies, except [ 13 , 14 ]), in aging animals [ 12 ], or in animals of unknown age [ 11 ], or do not include multiple cycles [ 13 , 14 ]. In addition, weight cycles are used that are too short to mimic human BW cycling [ 15 , 16 ].…”

Metabolic Reprogramming: Short-term Western Diet Exposure Induces Sustained Changes in Plasma Metabolites

“…https://doi.org/10.1101/554980 doi: bioRxiv preprint manifestations of weight gain in response to a WD. Interestingly, improved nutrition, dieting and weight loss do not invariably lead to a return to normal plasma metabolite concentrations, and these altered plasma levels of specific metabolites may be contributing to the increased cardiovascular disease risk observed in patients with repeated cycles of weight gain and loss (often termed yoyo dieting or weight cycling) in both females [10,11] and males [12]. However, the exact pattern of metabolic changes during this weight cycling has not been characterized, and it is unknown how quickly a WD exposure (with or without weight gain and subsequent loss) causes long-term changes.…”