The role for adipose tissue in weight regain after weight loss

Abstract

Weight regain after weight loss is a substantial challenge in obesity therapeutics. Dieting leads to significant adaptations in the homeostatic system that controls body weight, which promotes overeating and the relapse to obesity. In this review, we focus specifically on the adaptations in white adipose tissues that contribute to the biological drive to regain weight after weight loss. Weight loss leads to a reduction in size of adipocytes and this decline in size alters their metabolic and inflammatory characteristics in a manner that facilitates the clearance and storage of ingested energy. We present the hypothesis whereby the long-term signals reflecting stored energy and short-term signals reflecting nutrient availability are derived from the cellularity characteristics of adipose tissues. These signals are received and integrated in the hypothalamus and hindbrain and an energy gap between appetite and metabolic requirements emerges and promotes a positive energy imbalance and weight regain. In this paradigm, the cellularity and metabolic characteristics of adipose tissues after energy-restricted weight loss could explain the persistence of a biological drive to regain weight during both weight maintenance and the dynamic period of weight regain.

Influence of sleep restriction on weight loss outcomes associated with caloric restriction

“…Other factors such as the sensitivity of receptors may also complicate the issue. In the CR + SR group of our study, fasting leptin decreased by 24 per cent and ghrelin showed a trend for increase by 26 per cent, suggesting an energy deficiency state [36] which may reflect a greater energy need, and greater potential to initiate greater energy intake, which would put these individuals at risk for regaining the lost weight. These changes were absent in CR group; the absence of a significant reduction in leptin may in part be due to the small amount of fat mass loss which was not enough for the body to sense energy deficiency.…”

Glucocorticoid antagonism limits adiposity rebound and glucose intolerance in young male rats following the cessation of daily exercise and caloric restriction

“…Following weight loss from CR in overweight or obese individuals, nearly one-half of the weight is regained within one year (16). This weight regain is associated with a marked deterioration in whole body insulin sensitivity, which may occur via increased adipose tissue hypertrophy and hyperplasia, changes in neuroendocrine inputs to adipose tissue (43), and reductions in skeletal muscle insulin sensitivity (32). Although regular exercise attenuates the metabolic drive to regain weight after long-term weight loss in animal models (44), humans tend to relapse toward more sedentary behavior after lifestyle interventions (79).…”

“…The latter phenomenon is particularly intriguing, since CR in a setting of regular physical exercise may be a combined physiological stressor that sets the stage for adiposity rebound and insulin resistance when the food restriction and exercise stop. In a recent review (43), white adipocytes were highlighted for their role in contributing to weight regain, due in part to alterations in their metabolic and inflammatory characteristics that occur following weight loss, a process that is tightly linked to glucocorticoid (GC) biology. Weight cycling-induced glucose intolerance is paralleled by increased proinflammatory cytokine infiltration within adipose tissue, another process that could be linked to alterations in stress hormones (2).…”

Fisiopatología de la obesidad: Perspectiva actual

“…Pese a que una persona con obesidad presenta un mayor porcentaje de muerte adipocitaria, su reciclaje a partir de precursores es mayor 28 , llegando a un punto en el que la ganancia de peso, pese a las anormalidades metabólicas "in crescendo", da lugar a un aumento del número total de adipocitos (Figura 5) 56 . Si bien todavía es objeto de debate y no poca controversia, parece existir una suerte de mecanismo de defensa que tras una restricción calórica y pérdida de peso insta a su recuperación 57,58 . Esto dificultad en gran medida las estrategias encaminadas al mantenimiento del peso perdido.…”