Human Biology of Weight Maintenance after Weight Loss

Abstract

One year after losing weight, most people have regained a significant part of the lost weight. As such, weight regain after weight loss has a negative impact on human health. The risk for weight regain is determined by psychosocial and behavioral factors as well as by various physiological and molecular parameters. Here, the latter intrinsic factors are reviewed and assembled into four functional modules, two related to the energy balance and two related to resistance against weight loss. Reported genetic factors do not reveal additional functional processes. The modules form nodes in a network describing the complex interactions of intrinsically determined weight maintenance. This network indicates that after an initial weight loss persons with a high baseline fat mass will most easily succeed in maintaining weight, because they can lose fat without raising stress in adipocytes and at the same time spare fat-free mass. However, continued weight loss and weight maintenance requires extra measures like increased physical activity, limited energy intake and a fat-free sparing composition of the diet. Eventually, this network may help to design novel therapeutic measures based on preventing the return effect of specific plasma factors or by preventing the accumulation of adipocyte cellular stress.

Genetic Predictors of ≥5% Weight Loss by Multidisciplinary Advice to Severely Obese Subjects

“…The remodeling of the adipocyte ECM occurs during the development and growth of the fat depot [8] , but probably also when adipocytes shrink under conditions of calorie restriction [7] . The results from our study indicate that MMP2 rs1132896 (C/C genotype) is a predictor for high weight loss at 3 months.…”

“…Obesity is associated with hypertrophy of adipocytes demanding adaptation of the extracellular matrix (ECM), the outer protective layer of the cells [6] . Conversely, weight loss requires ECM adaptations, and inability of the adipocyte to respond adequately may lead to adipocyte cell stress, providing a risk factor for increased fat storage and weight regain [7,8] . Thus, variation in genes coding for components and modulators of the ECM and for fat storage capacity may play an important role in the weight loss response to a weight loss intervention.…”

Gender-specific genetic associations of polymorphisms in ACE, AKR1C2, FTO and MMP2 with weight gain over a 10-year period

“…Mechanistically, ACE may influence adipocyte ECM dynamics which is an important cellular parameter of weight loss and weight regain. In this respect, we have proposed that the ECM has a lower metabolic plasticity than the cell, leading during weight loss to the accumulation of stress between the shrinking cell and the rigid ECM, which forms a driving force for weight regain because restorage of fat may alleviate this stress (Mariman 2011(Mariman , 2012. The genetic interaction between FTO and ACE opens the possibility that also FTO may exert its effect somehow through the ECM dynamics.…”

Caloric Restriction for Treatment of Geriatric Obesity: Do the Benefits Outweigh the Risks?

“…Observational data also show proportionally more lean mass is lost during periods of weight loss than is gained during periods of weight gain or regain [90, 91], and that weight cycling increases the risk for physical disability [92]. Thus, since maintenance of lost weight is extremely difficult due, in part, to the biological adaptations that occur for the evolutionary purpose of defending existing energy stores [93, 94], an obesity treatment involving CR that leads to short-term weight loss followed by weight gain could accelerate sarcopenia over time in older adults. However, presently, there are no RCT data to support or refute this hypothesis.…”