The "metabolic syndrome" (MetS) is a clustering of components that reflect overnutrition, sedentary lifestyles, and resultant excess adiposity. The MetS includes the clustering of abdominal obesity, insulin resistance, dyslipidemia, and elevated blood pressure and is associated with other comorbidities including the prothrombotic state, proinflammatory state, nonalcoholic fatty liver disease, and reproductive disorders. Because the MetS is a cluster of different conditions, and not a single disease, the development of multiple concurrent definitions has resulted. The prevalence of the MetS is increasing to epidemic proportions not only in the United States and the remainder of the urbanized world but also in developing nations. Most studies show that the MetS is associated with an approximate doubling of cardiovascular disease risk and a 5-fold increased risk for incident type 2 diabetes mellitus. Although it is unclear whether there is a unifying pathophysiological mechanism resulting in the MetS, abdominal adiposity and insulin resistance appear to be central to the MetS and its individual components. Lifestyle modification and weight loss should, therefore, be at the core of treating or preventing the MetS and its components. In addition, there is a general consensus that other cardiac risk factors should be aggressively managed in individuals with the MetS. Finally, in 2008 the MetS is an evolving concept that continues to be data driven and evidence based with revisions forthcoming.

A dual-tracer approach (dietary 14C-palmitate and intraperitoneal 3H-H2O) was used to assess the trafficking of dietary fat and net retention of carbon in triglyceride depots during the first 24 h of weight regain. Obesity-prone male Wistar rats were allowed to mature under obesogenic conditions for 16 wk. One group was switched to ad libitum feeding of a low-fat diet for 10 wk (Obese group). The remaining rats were switched to an energy-restricted, low-fat diet for 10 wk that reduced body weight by 14% and were then assessed in energy balance (Reduced group), with free access to the low-fat diet (Relapse-Day1 group), or with a provision that induced a minor imbalance (+10 kcal) equivalent to that observed in obese rats (Gap-Matched group). Fat oxidation remained at a high, steady rate throughout the day in Obese rats, but was suppressed in Reduced, Gap-Matched, and Relapse-Day1 rats though 9, 18, and 24 h, respectively. The same caloric excess in Obese and Gap-Matched rats led to less fat oxidation over the day and greater trafficking of dietary fat to visceral depots in the latter. In addition to trafficking nutrients to storage, Relapse-Day1 rats had more small, presumably new, adipocytes at the end of 24 h. Dietary fat oxidation at 24 h was related to the phosphorylation of skeletal muscle acetyl-CoA carboxylase and fatty acid availability. These observations provide evidence of adaptations in the oxidation and trafficking of dietary fat that extend beyond the energy imbalance, which facilitate rapid, efficient regain during the relapse to obesity.

The impact of regular exercise on energy balance, fuel utilization, and nutrient availability, during weight regain was studied in obese rats, which had lost 17% of their weight by a calorie-restricted, low-fat diet. Weight reduced rats were maintained for 6 wk with and without regular treadmill exercise (1 h/day, 6 days/wk, 15 m/min). In vivo tracers and indirect calorimetry were then used in combination to examine nutrient metabolism during weight maintenance (in energy balance) and during the first day of relapse when allowed to eat ad libitum (relapse). An additional group of relapsing, sedentary rats were provided just enough calories to create the same positive energy imbalance as the relapsing, exercised rats. Exercise attenuated the energy imbalance by 50%, reducing appetite and increasing energy requirements. Expenditure increased beyond the energetic cost of the exercise bout, as exercised rats expended more energy to store the same nutrient excess in sedentary rats with the matched energy imbalance. Compared with sedentary rats with the same energy imbalance, exercised rats exhibited the trafficking of dietary fat toward oxidation and away from storage in adipose tissue, as well as a higher net retention of fuel via de novo lipogenesis in adipose tissue. These metabolic changes in relapse were preceded by an increase in the skeletal muscle expression of genes involved in lipid uptake, mobilization, and oxidation. Our observations reveal a favorable shift in fuel utilization with regular exercise that increases the energetic cost of storing excess nutrients during relapse and alterations in circulating nutrients that may affect appetite. The attenuation of the biological drive to regain weight, involving both central and peripheral aspects of energy homeostasis, may explain, in part, the utility of regular exercise in preventing weight regain after weight loss.