Pathways from weight fluctuations to metabolic diseases: focus on maladaptive thermogenesis during catch-up fat

Abstract

It has long been known that obesity is a high risk factor for cardiovascular diseases. In more recent years, the analysis of several large epidemiological databases has also revealed that, independently of excess weight, large fluctuations in body weight at some point earlier in life represent an independent risk factor for type 2 diabetes and hypertension -two major contributors to cardiovascular diseases. High cardiovascular morbidity and mortality have indeed been reported in men and women who in young adulthood experienced weight fluctuations (involving the recovery of body weight after weight loss due to disease, famine or voluntary slimming), or when weight fluctuations occurred much earlier in life and involved catch-up growth after fetal or neonatal growth retardation. This paper addresses the pathways from weight fluctuations to chronic metabolic diseases by focusing on the phenomenon of accelerated fat recovery (ie catch-up fat) after weight loss or growth retardation. Arguments are put forward that, during catch-up growth or weight recovery on our modern refined foods, the mechanisms of adaptive thermogenesis that regulate catch-up fat are pushed beyond the limits for which they were meant to operate and turn maladaptive. The consequences are enhanced susceptibilities towards skeletal muscle insulin resistance and overactive sympathetic activity, both of which are major contributors to the pathogenesis of chronic metabolic diseases. Since weight fluctuation earlier in life (independently of excess weight later in life) is an independent risk factor for metabolic diseases, the mechanisms by which body fat is acquired would seem to be at least as important as the consequences of excess fat per se in the pathogenesis of diabetes, hypertension and cardiovascular diseases. International Journal of Obesity (2002) 26, Suppl 2, S46 -S57. doi:10.1038=sj.ijo.0802127Keywords: obesity; diabetes; hypertension; catch-up growth; weight cycling; fetal programming Weight fluctuations through the agesCardiovascular diseases are well recognized to be among the most common debilitating complications of excess body fat. According to some reports, as many as 50% of obese people have high blood pressure and type 2 diabetes, which are both major contributors to their high predispositions to cardiovascular diseases.1,2 While restriction of energy intake and weight loss improve insulin sensitivity and lower blood pressure, the long-term prognosis of treatment is poor. In the vast majority of patients, the phase of weight loss is followed by a return towards the obese state, together with the associated metabolic complications and high cardiovascular risks. In fact, several lines of evidence suggest that the process of recovering body weight is itself an independent risk factor for the development of cardiovascular diseases.First, the analysis of several large epidemiological databases 3 -7 has revealed a higher cardiovascular morbidity and mortality in men and women who previously experienced marked fluctuations in body weigh...

Early adiposity rebound: causes and consequences for obesity in children and adults

“…The mechanisms by which body fat is acquired seem to be at least as important as the consequences of excess fat per se in the pathogenesis of diabetes, hypertension and cardiovascular diseases. 35 Consequently, as compared with a high BMI at 6 years or with centile crossing, 29 the early AR, which is associated with a particular BMI trajectory, has different implications and is likely associated with different environmental factors.…”

“…A relative energy deficit 66 may programme 'thrifty metabolism' and mechanisms of adaptative thermogenesis. 35 Lucas 67 proposed the term 'programming' for the process in which the programming stimulus exerts long-term effects when applied at a critical or sensitive period. Adaptation to low fat intake in early life may have adverse effects when, later in life, children will eat a more abundant high-fat diet.…”

Thrifty energy metabolism in catch-up growth trajectories to insulin and leptin resistance

“…Such increases in the ratio of fat mass to lean mass are also well documented in adults recovering body weight after weight loss due to a variety of conditions, including war-related famine, poverty-related under-nutrition, experimental starvation, anorexia nervosa and other pathophysiological 'hypermetabolic' conditions such as cancer, septic shock and AIDS. 42 Thus, a common denominator in many situations where there are large decreases in body weight followed by weight recovery -whether during growth or in adulthood -is that body fat is recovered at a disproportionately faster rate than lean tissue. Since this phenomenon of preferential catch-up fat still occurs in the absence of hyperphagia and on well-balanced diets, it underscores an elevated metabolic efficiency for catch-up fat as a fundamental physiological reaction to growth retardation.…”

Dynamic change in adiposity from fetal to postnatal life is involved in the metabolic syndrome associated with reduced fetal growth

“…In this perspective, the degree of catch-up growth, which indeed affects the severity of insulin resistance in SGA subjects, can be viewed as a surrogate index of the fetal damage. Indeed, it has been shown in various clinical situations of starvation including reduced fetal growth, that the catch-up growth phenomenon is more efficient for the fat mass than for the fat-free mass [29,30]. The association between low birthweight and insulin resistance in adulthood might therefore be explained by the very peculiar dynamic changes in adiposity observed in this situation.…”