Obesity is a major risk factor for diabetes,cardiovascular disease,and certain cancers.It arises from a chronic positive energy balance.This is usually due to unrestricted access to food in the context of genetic and epigenetic vulnerabilities.And an increasingly sedentary lifestyle.Over the past few decades,our understanding of the fluid and nervous systems that mediate energy balance control has greatly improved.However,our ability to formulate effective strategies to slow the current obesity epidemic has been hampered,mainly because we have limited knowledge of the resistance mechanisms of metabolic hormones such as leptin.Resistance to leptin is a sign of obesity,leptin is a key hormone for neuroendocrine control of energy balance.In the past few years,we have made tremendous progress in our in-depth research on the cellular pathways that disrupt the action of leptin.In this review,we discuss the molecular mechanisms of leptin resistance and how to use them as targets for obesity drug therapy.
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