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The percentage of energy from fat in diets has been thought to be an important determinant of body fat, and several mechanisms have been proposed. Comparisons of diets and the prevalence of obesity between affluent and poor countries have been used to support this relationship, but these contrasts are seriously confounded by differences in physical activity and food availability. Within areas of similar economic development, regional intake of fat and prevalence of obesity have not been positively correlated. Randomized trials are the preferable method to evaluate the effect of dietary fat on adiposity and are feasible because the number of subjects needed is not large. In short-term trials, a modest reduction in body weight is typically seen in individuals randomized to diets with a lower percentage of calories from fat. However, compensatory mechanisms appear to operate, because in randomized trials lasting >or=1 year, fat consumption within the range of 18% to 40% of energy appears to have little if any effect on body fatness. The weighted mean difference was -0.25 kg overall and +1.8 kg (i.e., less weight loss on the low-fat diets) for trials with a control group that received a comparable intensity intervention. Moreover, within the United States, a substantial decline in the percentage of energy from fat during the last 2 decades has corresponded with a massive increase in the prevalence of obesity. Diets high in fat do not appear to be the primary cause of the high prevalence of excess body fat in our society, and reductions in fat will not be a solution.

Physiologic responses to high and low leptin concentrations are strikingly asymmetrical. High concentrations often produce minimal effects, whereas low concentrations provoke strong counterregulatory responses. A model and rationale for the physiology is presented.

Background: The availability of biomedical literature in electronic format has made it possible to implement automatic text processing methods to expose implicit relationships among different documents, and more importantly, the functional relationships among the molecules and processes that these documents describe., Results: A computational strategy that identifies functionally related human genes by detecting the implicit relationships among the publications cited under each gene in the Online Mendelian Inheritance in Man (OMIM) was implemented. The implementation was based on a substantially modified version of the kernel document method. The improvements include assigning a calculated weight for a document to indicate its importance in establishing the relationship between two documents, and using multiple kernel documents to reflect the multiple functions of the same gene. An example of using this strategy to identify genes related to the apoptosis pathway in human was given., Conclusions: The results showed that this method can indeed produce meaningful results when applied to human genes.

Maintenance of a reduced body weight is associated with decreased 24-hour energy expenditure, and decreased circulating concentrations of leptin and thyroid hormones. To determine whether these adaptive metabolic and endocrine changes are partly leptin-mediated, we measured body composition, aspects of energy expenditure, and circulating concentrations of leptin and thyroid hormones in 4 subjects at 3 time points: 1.) Usual body weight; 2.) While stable at 10% reduced body weight; and 3.) During a 5-week period at 10% reduced body weight while receiving twice per day leptin injections that restored 8 AM circulating leptin concentrations to those seen at usual body weight. During maintenance of a 10% reduced body weight, circulating T3, T4, and leptin concentrations were decreased. All of these endocrine changes were reversed by administration of "replacement" doses of leptin (r-metHuLeptin). Indirect calorimetry, and subtle changes in body composition associated with leptin administration, were used to calculate the net change in stored calories and in 24-hour energy expenditure. Total energy expenditure increased in all subjects during r-metHuLeptin administration. These data indicate that decrease leptin concentrations resulting from loss of fat mass account for some aspects of the endocrine/metabolic phenotype associated with the weight-reduced state.

The relationship of leptin gene expression to adipocyte volume was investigated in lean 10-wk-old male C57BL/6J mice. mRNA levels for leptin, insulin receptor, glucocorticoid receptor, and tumor necrosis factor (TNF)-alpha in inguinal, epididymal, and retroperitoneal adipose tissues were quantified and related to adipocyte volume. Leptin mRNA levels were highly correlated with adipocyte volume within each fat depot. Multiple regression analysis of pooled data from the three depots showed that leptin mRNA levels were strongly correlated with adipocyte volumes (beta = 0.84, P < 0.001) and, to a smaller degree, with glucocorticoid receptor mRNA levels (beta = 0.36, P < 0.001). Depot of origin had no effect (P > 0.9). Rates of leptin secretion in vitro were strongly correlated with leptin mRNA levels (r = 0.89, P < 0.001). mRNA levels for TNF-alpha, insulin receptor, and glucocorticoid receptor showed no significant correlation with adipocyte volume. These results demonstrate that depot-specific differences in leptin gene expression are mainly related to the volumes of the constituent adipocytes. The strong correlation between leptin gene expression and adipocyte volume supports leptin's physiological role as a humoral signal of fat mass.