Acyl-ghrelin (AG), desacyl-ghrelin (DAG) and obestatin are all derived from the same gene transcript; however their plasma levels do not necessarily change in parallel. The influence of these peptides towards the development of obesity and their direct effects on adipocyte physiology has not been thoroughly investigated. This study was designed to evaluate the direct effects of peptides of the ghrelin family on preadipocyte proliferation, differentiation and adipocyte lipid and glucose metabolism in 3T3-L1 cells. 3T3 cells were treated with physiological peptide concentrations for 1 h to 9 days, and the relevant assays measured. In preadipocytes, AG, GHRP-6 and DAG stimulated proliferation, measured as (3)H-thymidine incorporation (up to 200%, P < 0.05), while all peptides stimulated differentiation (up to 300%, P < 0.01) as compared to standard differentiation conditions. In adipocytes, FA uptake was increased in a concentration-dependent manner especially with obestatin (three- to fourfold, P < 0.001) and DAG (three- to fivefold, P < 0.001). By contrast, glucose transport was unchanged. DAG and obestatin significantly decreased lipolysis measured as non-esterified fatty acid and glycerol release by 50%, P < 0.05-0.01 and 51%, P < 0.01, respectively. Interestingly, DAG stimulation of FA uptake was blocked with GHSR1 antagonist (D-lys(3))-GHRP-6 (P < 0.05), phospholipase C inhibitor U73122 and phosphatidylinositol-3-kinase inhibitor wortmannin (P < 0.001). Finally, in omental but not subcutaneous human adipose tissue, GHSR1 correlated with BMI (r = 0.549, P < 0.05) and insulin (r = 0.681, P < 0.01). Taken together, these results suggest that ghrelin-related peptides may directly affect adipose tissue metabolism.

Dairy products provide Ca and protein which may facilitate appetite control. Conversely, weight loss is known to increase the motivation to eat. This randomised controlled trial verified the influence of milk supplementation on appetite markers during weight loss. Low Ca consumer women participated in a 6-month energy-restricted programme (22508 kJ/d or 2600 kcal/d) and received either a milk supplementation (1000 mg Ca/d) or an isoenergetic placebo (n 13 and 12, respectively). Fasting appetite sensations were assessed by visual analogue scales. Anthropometric parameters and fasting plasma concentrations of glucose, insulin, leptin, ghrelin and cortisol were measured as well. Both groups showed a significant weight loss (P,0·0001). In the milksupplemented group, a time £ treatment interaction effect showed that weight loss with milk supplementation induced a smaller increase in desire to eat and hunger (P,0·05). Unlike the placebo group, the milk-supplemented group showed a lower than predicted decrease in fullness (2 17·1 v. 2 8·8; 212·7 v. 3·3 mm, P,0·05, measured v. predicted values, respectively). Even after adjustment for fat mass loss, changes in ghrelin concentration predicted those in desire to eat (r 0·56, P,0·01), hunger (r 0·45, P,0·05) and fullness (r 20·40, P, 0·05). However, the study did not show a between-group difference in the change in ghrelin concentration in response to the intervention. These results show that milk supplementation attenuates the orexigenic effect of body weight loss. Trial registration code: ClinicalTrials.gov NTC00729170.Key words: Milk: Appetite: Dairy products: Weight loss: Visual analogue scales: Obesity Body weight loss is generally recommended to decrease the risk and the severity of obesity-related comorbidities (1) . However, benefits that accompany weight reduction are often of short to medium term. This can particularly be explained by the occurrence of undesired side effects that result from fat mass loss and promote weight regain (2 -4) . For instance, weight-reducing programmes have been shown to increase the motivation to eat (5 -7) and, in the long run, this change can predict weight relapse (7) . A novel area of investigation consists of finding some satiating agents that may attenuate the increase in hunger induced by body weight loss.Some data suggest that Ca consumption could play a considerable role in the maintenance of a healthy body weight. Under free-living conditions, a negative association between daily Ca intake and adiposity markers has been observed (8) . Moreover, dietary Ca deficiency was recently reported to induce a greater increase in the risk of obesity than high fat intake or sedentariness (9) . Growing evidence also suggests that increasing Ca intake decreases the risk of obesity (10 -12) .Some mechanisms have been proposed to explain the potential influence of Ca consumption on body weight and fat mass. As reviewed by Major et al.

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BackgroundComplement 3 (C3), a key component of the innate immune system, is involved in early inflammatory responses. Acylation stimulating protein (ASP; aka C3adesArg), a C3 cleavage product, is produced in adipose tissue and stimulates lipid storage. We hypothesized that, depending on the diet, chronic ASP administration in C3−/− mice would affect lipid metabolism and insulin sensitivity via an adaptive adipose tissue inflammatory response.Methodology/Principal FindingsC3−/− mice on normal low fat diet (ND) or high fat diet (HFD) were chronically administered recombinant ASP (rASP) for 25 days via an osmotic mini-pump. While there was no effect on food intake, there was a decrease in activity, with a relative increase in adipose tissue weight on ND, and a shift in adipocyte size distribution. While rASP administration to C3−/− mice on a ND increased insulin sensitivity, on a HFD, rASP administration had the opposite effect. Specifically, rASP administration in C3−/− HFD mice resulted in decreased gene expression of IRS1, GLUT4, SREBF1 and NFκB in muscle, and decreased C5L2 but increased JNK, CD36, CD11c, CCR2 and NFκB gene expression in adipose tissue as well as increased secretion of proinflammatory cytokines (Rantes, KC, MCP-1, IL-6 and G-CSF). In adipose tissue, although IRS1 and GLUT4 mRNA were unchanged, insulin response was reduced.ConclusionThe effects of chronic rASP administration are tissue and diet specific, rASP administration enhances the HFD induced inflammatory response leading to an insulin-resistant state. These results suggest that, in humans, the increased plasma ASP associated with obesity and cardiovascular disease could be an additional factor directly contributing to development of metabolic syndrome, insulin resistance and diabetes.