Metabolic effects of diets differing in glycaemic index depend on age and endogenous GIP

Aims/hypothesis High- vs low-glycaemic index (GI) diets unfavourably affect body fat mass and metabolic markers in rodents. Different effects of these diets could be age-dependent, as well as mediated, in part, by carbohydrate-induced stimulation of glucose-dependent insulinotrophic polypeptide (GIP) signalling. Methods Young-adult (16 weeks) and aged (44 weeks) male wild-type (C57BL/6J) and GIP-receptor knockout (Gipr −/− ) mice were exposed to otherwise identical high-carbohydrate diets differing only in GI (20–26 weeks of intervention, n = 8–10 per group). Diet-induced changes in body fat distribution, liver fat, locomotor activity, markers of insulin sensitivity and substrate oxidation were investigated, as well as changes in the gene expression of anorexigenic and orexigenic hypothalamic factors related to food intake. Results Body weight significantly increased in young-adult high- vs low-GI fed mice (two-way ANOVA, p < 0.001), regardless of the Gipr genotype. The high-GI diet in young-adult mice also led to significantly increased fat mass and changes in metabolic markers that indicate reduced insulin sensitivity. Even though body fat mass also slightly increased in high- vs low-GI fed aged wild-type mice (p < 0.05), there were no significant changes in body weight and estimated insulin sensitivity in these animals. However, aged Gipr −/− vs wild-type mice on high-GI diet showed significantly lower cumulative net energy intake, increased locomotor activity and improved markers of insulin sensitivity. Conclusions/interpretation The metabolic benefits of a low-GI diet appear to be more pronounced in younger animals, regardless of the Gipr genotype. Inactivation of GIP signalling in aged animals on a high-GI diet, however, could be beneficial

Beta-carotene affects gene expression in lungs of male and female Bcmo1−/− mice in opposite directions

Molecular mechanisms triggered by high dietary beta-carotene (BC) intake in lung are largely unknown. We performed microarray gene expression analysis on lung tissue of BC supplemented beta-carotene 15,15′-monooxygenase 1 knockout (Bcmo1−/−) mice, which are—like humans—able to accumulate BC. Our main observation was that the genes were regulated in an opposite direction in male and female Bcmo1−/− mice by BC. The steroid biosynthetic pathway was overrepresented in BC-supplemented male Bcmo1−/− mice. Testosterone levels were higher after BC supplementation only in Bcmo1−/− mice, which had, unlike wild-type (Bcmo1+/+) mice, large variations. We hypothesize that BC possibly affects hormone synthesis or metabolism. Since sex hormones influence lung cancer risk, these data might contribute to an explanation for the previously found increased lung cancer risk after BC supplementation (ATBC and CARET studies). Moreover, effects of BC may depend on the presence of frequent human BCMO1 polymorphisms, since these effects were not found in wild-type mice

Fysiologische regulatie van de energiebalans - Een literatuuroverzicht

World-wide, the prevalence of overweight and obesity is increasing tremendously. Clues to the prevention of overweight may well be found in a better understanding of the physiological processes involved in the regulation of energy balance and factors that influence these processes, such as dietary factors and smoking. A review of available literature presented here showed the central nervous system to play an important role in the regulation of energy balance through effects on feeding behaviour and energy expenditure. The physiological response to weight loss seems to be more vigorous than to weight gain and may explain why it is so difficult to lose weight. Furthermore, increasing physical activity or maintaining it at high levels is important. The physiological regulatory mechanisms do not differ at low levels of energy expenditure from those at high levels, but it is easier to overeat at low levels of energy expenditure. Based on physiological mechanisms, diets low in energy density, low in fat, high in fibre and void of energy-containing liquids between meals constitute an effective strategy for preventing a positive energy balance or maintaining the weight reached after weight loss. The dynamic nature of research on the mechanisms involved in regulation of energy balance, however, may make it necessary to update this review in several years' time.Overgewicht en obesitas (ernstig overgewicht) komen wereldwijd en ook in Nederland steeds vaker voor. Overgewicht en obesitas zijn het gevolg van een langdurige positieve energiebalans. Kennis van de fysiologische mechanismen die de energiebalans reguleren en van factoren die deze regulatiemechanismen beinvloeden, zoals voedingsfactoren en roken, is noodzakelijk en levert mogelijk aanknopingspunten op die gebruikt kunnen worden ter voorkoming van overgewicht. Uit dit overzicht van beschikbare literatuur blijkt dat het centrale zenuwstelsel een belangrijke rol speelt bij de fysiologische regulatie van de energiebalans. Het beinvloedt zowel voedingsgedrag als energieverbruik. De fysiologische repons bij gewichtsverlies lijkt veel sterker te zijn dan de respons op gewichtstoename. Dit verklaart mogelijk waarom het zo moeilijk is gewicht te verliezen. Er is geen bewijs voor een veranderde fysiologische regulatie van de energiebalans bij een lage lichamelijke activiteit. Echter, bij een laag niveau van lichamelijk activiteit is het makkelijker te "overeten". Daarom is het belangrijk de lichamelijke activiteit op een hoog niveau te houden of te brengen. Gebaseerd op fysiologische regulatiemechanismen lijkt een voeding laag in energiedichtheid, laag in vet, rijk aan vezel en met een lage consumptie van energierijke dranken tussen de maaltijden door een effectieve strategie om een positieve energiebalans te voorkomen of om gewichtsverlies te handhaven. Het onderzoeksgebied dat de regulatie van de energiebalans bestudeerd is een zeer dynamisch veld. Dagelijks komt er nieuwe informatie bij. Daarom is het aan te bevelen om dit rapport over enkele jaren bij te werken

MONOSACCHARIDES IN POST-WEANING DIET OF YOUNG MICE PROGRAM BODY COMPOSITION AND FEEDING BEHAVIOUR IN ADULTHOOD

Nutrition in early life has permanent consequences affecting development and later-life health. In this study we investigated the potential of monosaccharides in the post-weaning diet to program adult metabolic health. Female and male C57BL/6JRccHsd mice were time-mated and fed a low-fat diet ad libitum. Litters were culled to six pups per nest and randomly assigned to foster dams. Mice were weaned onto one of three experimental diets containing 32 energy% as glucose (GLU), fructose (FRU) or an equimolar mixture of glucose and galactose (GAL). At six weeks of age, all mice received the same high-fat diet (HFD). Food intake, body weight, and body composition were measured biweekly. Whole-body metabolism was analysed towards the end of the post-weaning diet and during the last stretch of the high-fat feeding period in GLU and FRU mice. Additionally, an oral glucose tolerance test and a fasting-refeeding challenge as an indicator of metabolic flexibility were performed. At the end of the post-weaning intervention period, no significant differences were found in body weight or lean mass across all dietary groups, and in 24-hour energy expenditure and substrate oxidation between GLU and FRU. At week 15, cumulative food intake, body weight, and fat mass were significantly lower in GAL females compared to GLU females. Glucose tolerance in all groups, and energy expenditure, fuel utilization, and metabolic flexibility between GLU and FRU did not reveal programmed differences in metabolic phenotype. None of the parameters studied indicated long-lasting effects in males. This study provides evidence of the potential of galactose in the post-weaning diet to program a reduction in food intake resulting in lower fat mass during adulthood. Our findings highlight the relevance of carbohydrates as a dietary intervention target for future clinical studies in the field of metabolic programming.Acknowledgements: Financially supported by NWO-Applied and Technical Sciences grant 1350