Obesity triggers a low-grade systemic inflammation, which plays an important role in the development of obesity-associated metabolic diseases. In searching for links between lipid accumulation and chronic inflammation, we examined invariant natural killer T (iNKT) cells, a subset of T lymphocytes that react with lipids and regulate inflammatory responses. We show that iNKT cells respond to dietary lipid excess and become activated before or at the time of tissue recruitment of inflammatory leukocytes, and that these cells progressively increase proinflammatory cytokine production in obese mice. Such iNKT cells skew other leukocytes toward proinflammatory cytokine production and induce an imbalanced proinflammatory cytokine environment in multiple tissues. Further, iNKT cell deficiency ameliorates tissue inflammation and provides protection against obesity-induced insulin resistance and hepatic steatosis. Conversely, chronic iNKT cell stimulation using a canonical iNKT cell agonist exacerbates tissue inflammation and obesityassociated metabolic disease. These findings place iNKT cells into the complex network linking lipid excess to inflammation in obesity and suggest new therapeutic avenues for obesity-associated metabolic disorders.cluster of differentiation 1d | glycolipid-reactive T cells | alpha-galactosylceramide | obesity-induced inflammation

The patterns of secretion of ghrelin and PYY in our study of prepubertal children suggest that they may play a role in the effectiveness of high-protein/low-carbohydrate diets in promoting weight loss.

objective: Ghrelin and peptide YY (PYY) are two gut hormones that have effects on appetite. Our objectives were to characterize the patterns of secretion of these hormones in response to feeding in school-age children and determine whether there were differences between normal weight (NW) and overweight (OW) subjects. Methods and Procedures: This was a cross-sectional study at one tertiary care center. Subjects were 7-to 11-year-old healthy NW and OW volunteers recruited from local advertisements. Following an overnight fast, the subjects were given a standardized breakfast and lunch and had nine hourly blood samples for total ghrelin and total PYY. We assessed whether ghrelin and PYY levels changed from the preprandial to postprandial state and corresponded to reported hunger/satiety. Results: Hunger ratings were similar between the two groups throughout the study period. Ghrelin was not suppressed after eating, did not rise prior to the next meal, and did not correspond to hunger ratings in either group. PYY increased postprandially and decreased preprandially in the NW group, but OW children exhibited this pattern for only part of the day. PYY levels incompletely corresponded to reported satiety in the OW group. Discussion: Mixed meal consumption had little effect on ghrelin secretion and a variable effect on PYY secretion in young children in our study. Differences that were observed between the groups do not suggest that an abnormality in their secretion contributes to the development of obesity.

Background/Objectives Hypothalamic obesity (HO) is a common complication of hypothalamic tumors and effective therapies are lacking. The objective of this pilot study was to investigate changes in body weight before and during treatment with exenatide. Subjects/Methods This was a prospective, open-label 52-week pilot study of exenatide (10 mcg b.i.d.) in adults with HO. Ten patients enrolled and 8 completed the study. Study measures included indirect calorimetry, body composition, buffet meals, diet recall, actigraphy and hormone assays. Results Participants were obese with a baseline weight of 137.2 ± 37.6 kg. Exenatide therapy was well tolerated. Change in weight with exenatide therapy was not significant (−1.4 ± 4.3 kg [95% CI −2.2 to 4.9], p=0.40) but 6 of 8 completers lost weight (−6.2 to −0.2 kg). Participants reported significantly lower intake on food recall during treatment compared with baseline (7837.8 ± 2796.6 vs. 6258.4 ± 1970.7 kJ [95% CI −2915.8 to −242.6], p= 0.027) but there was no change in intake during buffet meals. Conclusions We did not observe significant weight loss in patients with HO treated with exenatide but 75% of completers had stable or decreasing weight. Further studies are needed to evaluate weight loss efficacy in patients with HO.

ContextPatients with pseudohypoparathyroidism type 1a (PHP-1a) develop early-onset obesity. The abnormality in energy expenditure and/or energy intake responsible for this weight gain is unknown.ObjectiveThe aim of this study was to evaluate energy expenditure in children with PHP-1a compared with obese controls.PatientsWe studied 6 obese females with PHP-1a and 17 obese female controls. Patients were recruited from a single academic center.MeasurementsResting energy expenditure and thermogenic effect of a high fat meal were measured using whole room indirect calorimetry. Body composition was assessed using whole body dual energy x-ray absorptiometry. Fasting glucose, insulin and hemoglobin A1C were measured.ResultsChildren with PHP-1a had decreased resting energy expenditure compared with obese controls (P <0.01). After adjustment for fat free mass, the PHP-1a group’s resting energy expenditure was 346.4 kcals/day less than obese controls (95% CI [−585.5 to −106.9], P <0.01). The thermogenic effect of food, expressed as percent increase in postprandial energy expenditure over resting energy expenditure, was lower in PHP-1a patients than obese controls but did not reach statistical significance (absolute reduction of 5.9%, 95% CI [−12.2% to 0.3%], P = 0.06).ConclusionsOur data indicate that children with PHP-1a have decreased resting energy expenditure compared with obese controls and that may contribute to the development of obesity in these children. These patients may also have abnormal diet-induced thermogenesis in response to a high fat meal. Understanding the causes of obesity in PHP-1a may allow for targeted nutritional or pharmacologic treatments in the future.