Weight loss is coupled with improvements to affective state in obese participants engaged in behavior change therapy based on incremental, self-selected "small changes".

The aim of this study was to investigate the effects of a group behavior change intervention involving self-selected, contextualized, and mediated goal setting on anthropometric, affective, and dietary markers of health. It was hypothesized that the intervention would elicit changes consistent with accepted health recommendations for obese individuals. A rolling program of 12-week "Small Changes" interventions during 24 months recruited 71 participants; each program accommodated 10 to 13 adults (body mass index [BMI] ≥ 30 kg/m²). Fifty-eight participants completed Small Changes. Repeated measures were made at baseline, 6 and 12 weeks. Anthropometric measures included height and weight (to calculate BMI), body composition, waist circumference, and blood pressure. Affective state was monitored using relevant validated questionnaires. Dietary assessment used 3-day household measures food diaries with Schofield equations to monitor underreporting. Relevant blood measures were recorded throughout. Across the measurement period, Small Changes elicited a significant reduction in body weight (baseline, 102.95 ± 15.47 vs 12 weeks 100.09 ± 16.01 kg, P < .0005), coupled with associated significant improvements in BMI, body fat percentage, and waist circumference measures. There were additional significant positive changes in measures of affective state including general well-being (baseline, 58.92 ± 21.22 vs 12 weeks 78.04 ± 14.60, P < .0005) and total mood disturbance (baseline, 31.19 ± 34.03 vs 12 weeks 2.67 ± 24.96, P < .0005). Dietary changes that occurred were largely consistent with evidenced-based recommendations for weight management and included significant reductions in total energy intake and in fat and saturated fat as a proportion of energy. The Small Changes approach can elicit a range of health-orientated benefits for obese participants, and although further work is needed to ascertain the longevity of such effects, the outcomes from Small Changes are likely to help inform health professionals when framing the future of weight management. Long-term follow-up of Small Changes is warranted.

Heme-binding protein HRG-1 is induced by insulin-like growth factor I and associates with the vacuolar H+-ATPase to control endosomal pH and receptor trafficking.

Endocytosis and trafficking of receptors and nutrient transporters are dependent on an acidic intra-endosomal pH that is maintained by the vacuolar H(+)-ATPase (V-ATPase) proton pump. V-ATPase activity has also been associated with cancer invasiveness. Here, we report on a new V-ATPase-associated protein, which we identified in insulin-like growth factor I (IGF-I) receptor-transformed cells, and which was separately identified in Caenorhabditis elegans as HRG-1, a member of a family of heme-regulated genes. We found that HRG-1 is present in endosomes but not in lysosomes, and it is trafficked to the plasma membrane upon nutrient withdrawal in mammalian cells. Suppression of HRG-1 with small interfering RNA causes impaired endocytosis of transferrin receptor, decreased cell motility, and decreased viability of HeLa cells. HRG-1 interacts with the c subunit of the V-ATPase and enhances V-ATPase activity in isolated yeast vacuoles. Endosomal acidity and V-ATPase assembly are decreased in cells with suppressed HRG-1, whereas transferrin receptor endocytosis is enhanced in cells that overexpress HRG-1. Cellular uptake of a fluorescent heme analogue is enhanced by HRG-1 in a V-ATPase-dependent manner. Our findings indicate that HRG-1 regulates V-ATPase activity, which is essential for endosomal acidification, heme binding, and receptor trafficking in mammalian cells. Thus, HRG-1 may facilitate tumor growth and cancer progression.