Since the discovery of leptin in 1994, a considerable amount of research has focused on leptin as a central regulator of body weight. In the animal model, research has demonstrated leptin action through hypothalamic centres altering both satiety and energy expenditure. In contrast to animal studies, it is unlikely that leptin functioning in the human system exerts such a profound role in body weight regulation. Human studies suggest that leptin levels are strongly correlated with both percentage fat mass and body mass index, in accordance with the proposed 'lipostatic theory'. Current research suggests the existence of a unique inter-relationship between dietary fat, leptin expression and leptin action within the peripheral system. More specifically, it has been demonstrated that polyunsaturated fatty acid (PUFA) intake influences adipose tissue expression of leptin, and of several lipogenic enzymes and transcription factors. In addition, leptin stimulates triglyceride depletion in white adipose tissue without increasing free fatty acid release, thus favouring fatty acids versus glucose as a fuel source. Recent studies suggest that the reduction in adipose hypertrophy observed with n-3 PUFA-containing fish oil feeding might involve a leptin-specific process. A large amount of evidence supports direct functioning of leptin in peripheral lipid metabolism in vivo and in vitro. It is possible that PUFAs will maintain an efficient level of circulating leptin, thus preventing leptin insensitivity and weight gain. There has been much recent progress in clinical leptin research, from energy expenditure to leptin analogue efficacy; the purpose of the present review is to summarize our current understanding of leptin functioning.

To investigate whether dietary fatty acid (FA) composition and energy restriction (ER) interactively influence obese ( ob ) gene expression, rats consumed diets containing beef tallow, safflower, or fish oil ad libitum (AL) or at 60% AL intake. Circulating leptin concentrations were higher ( P Ͻ 0.0001) after AL feeding, but were not influenced by dietary fat. ER decreased ( P Ͻ 0.0001) weight gain and visceral adipose weight, which were positively correlated ( r ‫؍‬ 0.40 P Ͻ 0.001, r ‫؍‬ 0.58 P Ͻ 0.0001) with circulating leptin levels. Visceral adipose ob mRNA levels were greater in animals fed unsaturated fats, particularly safflower oil, which had the highest ob mRNA levels. Circulating leptin levels did not parallel ob mRNA levels, except for the greater abundance detected in AL adipose in comparison to ER animals. In addition, visceral FA profiles reflected dietary fat source and were influenced by an interaction of dietary fat and energy. These data demonstrate that dietary fat, particularly from a plant or marine source, and ER interactively influence ob mRNA levels; however, alterations in ob mRNA do not confer changes in circulating leptin, with the exception of ER, which is a key determinant. Thus, dietary intake is an important regulator of leptin production; however, the significance of these modest changes in diet-induced obese animals requires further study.