An inverse relationship between Ca intake and BMI has been found in several studies. It has been suggested that Ca affects adipocyte metabolism via suppressing 1,25-dihydroxycholecalciferol (1,25(OH) 2 -D 3 ) and decreases fat absorption. We studied the effect of Ca and milk proteins (whey and casein) on body weight in C57Bl/6J mice. Male mice, age 9 weeks, were divided into three groups (ten mice per group) receiving modified high-fat (60 % of energy) diets. Two groups received a high-Ca diet (1·8 % calcium carbonate (CaCO 3 )), with casein or whey protein (18 % of energy), and one group received a low-Ca diet (0·4 % CaCO 3 ) with casein for 21 weeks. Food intake was measured daily and body weight twice per week. Body fat content (by dual-energy X-ray absorptiometry) of all mice and faecal Ca and fat excretion of seven mice/group were measured twice during the study. Final body weight (44·1 (SEM 1·1) g) and body fat content (41·6 (SEM 0·6) %) were significantly lower (P, 0·05) in the high-Ca whey group than in the low-Ca casein group (48·1 (SEM 0·8) g and 44·9 (SEM 0·8) %). Body weight and body fat content of the high-Ca casein group did not differ significantly from the low-Ca casein group even though serum 1,25(OH) 2 -D 3 levels were significantly lower (P,0·001) in both high-Ca groups than in the low-Ca casein group. Thus changes in serum 1,25(OH) 2 -D 3 do not seem to affect body weight in this animal model. There was a significant difference in fat excretion between the high-Ca whey and low-Ca casein groups (3·9 (SEM 0·9) % in the high-Ca whey v. 1·4 (SEM 0·2) % in the low-Ca casein group; P, 0·05), which may partly explain the effect on body weight.

Obesity is frequently associated with endothelial dysfunction. We hypothesized that high-fat feeding dysregulates the balance between endothelial derived nitric oxide and superoxide formation. Furthermore, we examined whether caloric restriction could reverse the detrimental vascular effects related to obesity. Male C57Bl/6 mice were fed with normal-fat diet (fat 17%) or high-fat diet (fat 60%) for 150 days. After establishment of obesity at day 100, a subgroup of obese mice were put on caloric restriction (CR) (70% of ad libitum energy intake) for an additional 50 days. At day 100, aortic rings from obese mice receiving high-fat diet showed impaired endothelium-dependent vasodilation in response to acetylcholine (ACh). Caloric restriction reversed high-fat diet-induced endothelial dysfunction. At day 150, impaired vasodilatory responses to ACh in obese mice without caloric restriction were markedly improved by preincubation with the tetrahydrobiopterin (BH(4)) precursor sepiapterin and L-arginine, a substrate for endothelial nitric oxide synthase (eNOS). Additionally, inhibition of vascular arginase by L-norvaline partially, and superoxide scavenging by Tiron completely, restored endothelial cell function. Obese mice showed increased vascular superoxide production, which was diminished by endothelial denudation, pretreated of the vascular rings with apocynin (an inhibitor of reduced nicotinamide adenine dinucleotide phosphate [NADPH] oxidase), oxypurinol (an inhibitor of xanthine oxidase), N(G)-nitro-L-arginine methyl ester (LNAME; an inhibitor of eNOS), or by adding the BH(4) precursor sepiapterin. Caloric restriction markedly attenuated vascular superoxide production. In obese mice on CR, endothelial denudation increased superoxide formation whereas vascular superoxide production was unaffected by L-NAME. Western blot analysis revealed decreased phosphorylated eNOS (Ser1177)-to-total eNOS expression ratio in obese mice as compared to lean controls, whereas the phospho-eNOS/NOS ratio in obese mice on CR did not differ from the lean controls. In conclusion, the present study suggests that caloric restriction reverses obesity induced endothelial dysfunction and vascular oxidative stress, and underscores the importance of uncoupled eNOS in the pathogenesis.

The aim of the study was to compare the effect of different whey protein-containing high-Ca diets on weight loss and weight regain in a model of diet-induced obesity. Obesity was induced in C57BL/6J mice with a high-fat (60 % of energy) diet. Weight loss by energy restriction was performed on four different high-Ca diets (1·8 % CaCO 3 ) containing different whey proteins (18 % of energy): a-lactalbumin (ALA), b-lactoglobulin (BLG), lactoferrin (LF) and whey protein isolate (WPI). After 7 weeks of energy restriction some of the mice were killed and the rest were fed with the same diets ad libitum for 7 weeks. The mice on the LF diet lost significantly more weight than mice on the WPI diet. The body fat content in the ALA and LF groups was significantly lower than in the WPI group (P, 0·05) and the LF group differed significantly even from the BLG group (P,0·05). Ad libitum feeding after weight loss resulted in weight regain in all groups and only the ALA diet significantly reduced fat accumulation during weight regain. The weight regain was most pronounced in the LF group, but the adipocyte size was still significantly smaller than in the other groups. There were no differences in food intake or apparent fat digestibility between the groups. It can be concluded that a high-Ca diet with ALA significantly improves the outcome of weight loss and subsequent weight regain during the feeding of a high-fat diet in C57BL/6J mice, in comparison with WPI.

A low intensity home based exercise program combined with post-exercise milk protein supplementation is feasible despite some gastrointestinal complaints and seems effective in improving the muscle mass and functions of older persons with a inflammatory disease. Further studies are needed to establish, whether and to what extent the use of leucine-enriched whey products prevent or treat age-associated sarcopenia and whether they are superior to the present commercial milk products.