Obesity, Metabolic Syndrome and Disorders of Energy Balance

Energy balance is complex and regulated by neuroendocrine homeostatic mechanisms (primarily the leptin melanocortin pathway) and non-homeostatic mechanisms (such as hedonic reward pathways). The central nervous system plays a key role in controlling both energy intake and expenditure in response to peripheral cues of energy status. Imbalances in energy intake relative to expenditure can occur because of multiple etiologies (including biologic, behavioral, and environmental factors) and ultimately lead to obesity or underweight, both of which result in further derangements of endocrine function. Childhood obesity has become a serious global health problem, and pediatric endocrinologists are receiving increasing numbers of referrals for the management of obesity and related endocrine disorders, such as type 2 diabetes and polycystic ovarian syndrome. A classic endocrinopathy (glucocorticoid excess or deficiencies in thyroid or growth hormone), genetic obesity syndrome (e.g., Prader-Willi syndrome, ciliopathy, or monogenic leptin melanocortin pathway mutation), or hypothalamic lesion is important to rule out but is not generally found to be the cause of abnormal weight gain. However, recognizing obesity as a universal form of perhaps a more subtle chronic endocrine dysfunction that includes deficits in leptin melanocortin signaling and resistance to insulin action is critical for addressing obesity as a pathologic condition that will often require lifelong treatment. Conversely, cachexia can also be viewed as a condition driven by neuroendocrine dysfunction. Thus understanding energy balance and the disorders that impair its regulation are vital for identifying targeted approaches for the prevention and treatment of both obesity and underweight.