Abstract
Leptin is a principal adipose-derived hormone mostly implicated in the regulation of energy balance through the activation of anorexigenic neuronal pathways. Comprehensive studies have established that the maintenance of certain concentrations of circulating leptin is essential to avoid an imbalance in nutrient intake. Indeed, genetic modifications of the leptin/leptin receptor axis and the obesogenic environment may induce changes in leptin levels or action in a manner that accelerates metabolic dysfunctions, resulting in a hyperphagic status and adipose tissue expansion. As a result, a vicious cycle begins wherein hyperleptinaemia and leptin resistance occur, in turn leading to increased food intake and fat enlargement, which is followed by leptin overproduction. In addition, in the context of obesity, a defective thermoregulatory response is associated with impaired leptin signalling overall within the ventromedial nucleus of the hypothalamus. These recent findings highlight the role of leptin in the regulation of adaptive thermogenesis, thus suggesting leptin to be potentially considered as a new thermolipokine. This review provides new insight into the link between obesity, hyperleptinaemia, leptin resistance and leptin deficiency, focusing on the ability to restore leptin sensitiveness by way of enhanced thermogenic responses and highlighting novel anti-obesity therapeutic strategies.
Highlights
Obesity is considered a chronic medical condition whose pathogenesis has a multifactorial origin
It is known that suppression of cytokine signalling 3 (SOCS3) is able to block LepRb signalling and, since hyperleptinaemia is characterised by high hypothalamic SOCS3 levels, it was hypothesised that the upregulation of SOCS3 in leptin-responsive cells is, a potential mechanism for leptin resistance, a characteristic feature of human obesity [75]
Obesity might be associated with hyperleptinaemia, which reflects a state of leptin resistance involving leptin and molecular pathways downstream of leptin receptor (LEPR), or with leptin deficiency, which might be either complete or heterozygous (Figures 1 and 2)
Summary
Obesity is considered a chronic medical condition whose pathogenesis has a multifactorial origin. When an imbalance between energy consumption and disposal occurs, adipose tissues lose their ability to reservoir fatty acids, promoting lipid spillover into ectopic organs To avoid these unfavourable metabolic consequences, a plethora of endocrine hormones are normally released to preserve energy homeostasis. Long-term exposure to leptin overload, can result in a still ill-defined state of ‘leptin resistance’ wherein abnormal leptin receptor (LEPR) activity is observed. In this scenario, leptin-dependent anorexic effects are lacking in the presence of persistent leptin stimulation due to the existence of a potent feedback mechanism that relies on the induced suppression of cytokine signalling 3 (SOCS3) and protein tyrosine phosphatase (PTP1B). We will discuss current knowledge regarding the emerging thermogenic role of leptin and related mechanisms in an obesogenic environment, as well as the effects of potentiating leptin signalling as an anti-adiposity strategy
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
