Leptin: in search of role(s) in human physiology and pathophysiology

Abstract

Obesity, a health problem reaching epidemic proportions in western countries, is an important risk factor for the most frequent diseases in the western world, i.e. diabetes, hypertension, cardiovascular diseases and certain types of cancer. Thus, significant research efforts have been focusing on its aetiology, prevention and treatment. The recent discovery of leptin (from the Greek word leptos: i.e. thin), the product of the ob gene (Zhang et al., 1994), has greatly advanced our understanding of body adiposity and energy balance regulation. This hormone, produced mainly by adipose tissue, conveys to the brain information about the size of energy stores and activates hypothalamic centres that regulate energy intake and expenditure (Flier, 1997). Moreover, leptin affects several neuroendocrine mechanisms and regulates multiple hypothalamicpituitary axes (Flier, 1997). The realization that adipose tissue is not simply a storage depot, but also an important endocrine gland, has created new opportunities for the investigation and, possibly, treatment of diseases such as obesity and eating disorders.In this review, we discuss the biology of leptin secretion and regulation, as well as our current knowledge of the role leptin plays in various physiological and pathophysiological states. Although most available research studies have been based on animal models, a substantial amount of information has been accumulated over the last 3 years on the role of leptin in humans. Thus, this article mainly focuses on our current knowledge about the role of leptin in human physiology and pathophysiology. Finally, some of the important unanswered questions about leptin physiology are discussed and future directions for leptin research are suggested.

Leptin-deficient (ob/ob) mice are protected from T cell-mediated hepatotoxicity: Role of tumor necrosis factor α and IL-18

“…Leptin, initially discovered as a regulator of food intake and energy expenditure, is emerging as a pleiotropic molecule involved in a variety of physiological and pathological functions (43). Alterations in leptin levels and͞or in the responsiveness to leptin have been reported not only during starvation and obesity, but also in patients affected by diabetes, renal failure, hypothyroidism, and AIDS (43).…”

“…Alterations in leptin levels and͞or in the responsiveness to leptin have been reported not only during starvation and obesity, but also in patients affected by diabetes, renal failure, hypothyroidism, and AIDS (43). T lymphocytes and cytokines are critical mediators of hepatic inflammation in patients affected by viral, allergic, autoimmune, and possibly alcoholic liver disease (44)(45)(46)(47).…”

Metabolic syndrome and its components are associated with increased thyroid volume and nodule prevalence in a mild-to-moderate iodine-deficient area

“…Leptin regulates TRH expression (28). Recent evidence has suggested that the relationship between leptin levels and FM is curvilinear, so that leptin secretion increases exponentially with increasing FM (29). Insulin also increases total leptin levels (30).…”

Leptina: o diálogo entre adipócitos e neurônios

“…Os trabalhos iniciais sobre leptina versavam sobre seus efeitos biológicos mais evidentes: diminuição do peso e da ingestão alimentar (2). Posteriormente, descobriu-se que a leptina atuava em sistemas fisiológicos independentes do controle de energia (3). Recentemente, ensaios clínicos com leptina recombinante fecharam um ciclo de investigações que começaram com modelos animais de obesidade e chegaram até o tratamento da obesidade em humanos (4,5).…”