Childhood obesity has emerged as an important public health problem in the United States and other countries in the world. Currently 1 in 3 children in the United States is afflicted with overweight or obesity. The increasing prevalence of childhood obesity is associated with emergence of comorbidities previously considered to be "adult" diseases including type 2 diabetes mellitus, hypertension, nonalcoholic fatty liver disease, obstructive sleep apnea, and dyslipidemia. The most common cause of obesity in children is a positive energy balance due to caloric intake in excess of caloric expenditure combined with a genetic predisposition for weight gain. Most obese children do not have an underlying endocrine or single genetic cause for their weight gain. Evaluation of children with obesity is aimed at determining the cause of weight gain and assessing for comorbidities resulting from excess weight. Family-based lifestyle interventions, including dietary modifications and increased physical activity, are the cornerstone of weight management in children. A staged approach to pediatric weight management is recommended with consideration of the age of the child, severity of obesity, and presence of obesity-related comorbidities in determining the initial stage of treatment. Lifestyle interventions have shown only modest effect on weight loss, particularly in children with severe obesity. There is limited information on the efficacy and safety of medications for weight loss in children. Bariatric surgery has been found to be effective in decreasing excess weight and improving comorbidities in adolescents with severe obesity. However, there are limited data on the long-term efficacy and safety of bariatric surgery in adolescents. For this comprehensive review, the literature was scanned from 1994 to 2016 using PubMed using the following search terms: childhood obesity, pediatric obesity, childhood overweight, bariatric surgery, and adolescents.

BMI has high specificity but low sensitivity to detect excess adiposity and fails to identify over a quarter of children with excess body fat percentage.

The signs and symptoms of Graves' ophthalmopathy (GO) result from increased volume of the orbital contents, including adipose, connective, and extraocular muscle tissues. We wanted to determine whether the expanded adipose tissue volume might be in part attributable to de novo adipogenesis. We measured levels of mRNA encoding leptin, adiponectin, peroxisome proliferator-activated receptor gamma (PPAR gamma), preadipocyte factor-1, and TSH receptor (TSHr) genes in orbital adipose tissues from GO patients (n = 22) and normal individuals (n = 18) and in orbital preadipocyte cultures derived from GO patients (n = 6) and normal subjects (n = 3) using quantitative real-time RT PCR. We found increased leptin, adiponectin, PPAR gamma, and TSHr expression in GO compared with normal orbital tissue samples, with positive correlations in the GO tissues between TSHr and leptin, adiponectin and PPAR gamma. In vitro differentiation of GO and normal preadipocytes resulted in enhanced adiponectin, leptin, and TSHr expression, with greater expression of the latter two genes in the GO cultures. These results suggest that de novo adipogenesis within orbital tissues with parallel enhanced expression of TSHr may be important in the pathogenesis of GO, and that potential therapies for GO might include inhibition of the adipogenic pathway.

Graves' ophthalmopathy (GO) is characterized by expanded volume of the orbital tissues associated with elevated serum levels of TSH receptor (TSHR) autoantibodies. Because previous studies have demonstrated evidence of adipogenesis within the GO orbit, we sought to determine whether M22, a human monoclonal antibody directed against TSHR, enhances adipogenesis in orbital fibroblasts from patients with GO and, if so, to identify signaling mechanisms involved. GO orbital fibroblast cultures (n=10) were treated for 10 days with bovine TSH (1 or 10·0 U/l) or M22 (1 or 10 ng/ml) in serum-free adipocyte differentiation medium. Some cultures also received a phosphoinositide 3-kinase (PI3K) inhibitor or an inhibitor of cAMP production. In other experiments, confluent cultures (n=8) were treated for between 1 and 30 min with TSH (0·1–10·0 U/l) or M22 (0·1–100 ng/ml) with measurement of cAMP production or levels of phosphorylated AKT (pAKT). We found levels of adiponectin, leptin, and TSHR mRNA to be increased in GO cultures treated for 10 days with either M22 (2·6 mean fold ±0·7; P=0·03) or TSH (13·2±5·8-fold, P=0·048). In other studies, M22 and TSH stimulated cAMP production and pAKT levels in GO cells. Inhibition of PI3K activity during 10 days in culture decreased the levels of M22-stimulated mRNA encoding adiponectin (67±12%; P=0·021), as well as adiponectin and CCAAT/enhancer-binding protein α protein levels. In conclusion, M22 is a pro-adipogenic factor in GO orbital preadipocytes. This antibody appears to act via the PI3K signaling cascade, suggesting that inhibition of PI3K signaling may represent a potential novel therapeutic approach in GO.

Lower circulating levels of Spexin in obese children compared with their normal-weight counterparts and the ability to discriminate obese and normal-weight groups based on Spexin concentration enabled us to suggest a potential role for this novel peptide in childhood obesity. The clinical significance of these findings needs additional investigation.

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In euthyroid children without a history of hypo- or hyperthyroidism, increasing levels of TSH and decreasing levels of free T4 are associated with higher triglyceride levels and elevated markers of insulin resistance. Whether these findings carry implications regarding optimal TSH levels in children at increased risk for cardiovascular disease awaits further study.

These results support the concept that orbital adipogenesis is enhanced in GO and suggest that elevated levels of sFRP-1 in the GO orbit may be involved in stimulating this pathogenic process.