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

Knockout of the Bcmo1 gene results in an inflammatory response in female lung, which is suppressed by dietary beta-carotene

Beta-carotene 15,15′-monooxygenase 1 knockout (Bcmo1−/−) mice accumulate beta-carotene (BC) similarly to humans, whereas wild-type (Bcmo1+/+) mice efficiently cleave BC. Bcmo1−/− mice are therefore suitable to investigate BC-induced alterations in gene expression in lung, assessed by microarray analysis. Bcmo1−/− mice receiving control diet had increased expression of inflammatory genes as compared to BC-supplemented Bcmo1−/− mice and Bcmo1+/+ mice that received either control or BC-supplemented diets. Differential gene expression in Bcmo1−/− mice was confirmed by real-time quantitative PCR. Histochemical analysis indeed showed an increase in inflammatory cells in lungs of control Bcmo1−/− mice. Supported by metabolite and gene-expression data, we hypothesize that the increased inflammatory response is due to an altered BC metabolism, resulting in an increased vitamin A requirement in Bcmo1−/− mice. This suggests that effects of BC may depend on inter-individual variations in BC-metabolizing enzymes, such as the frequently occurring human polymorphisms in BCMO1

Beta-Carotene Reduces Body Adiposity of Mice via BCMO1

Evidence from cell culture studies indicates that β-carotene-(BC)-derived apocarotenoid signaling molecules can modulate the activities of nuclear receptors that regulate many aspects of adipocyte physiology. Two BC metabolizing enzymes, the BC-15,15′-oxygenase (Bcmo1) and the BC-9′,10′-oxygenase (Bcdo2) are expressed in adipocytes. Bcmo1 catalyzes the conversion of BC into retinaldehyde and Bcdo2 into β-10′-apocarotenal and β-ionone. Here we analyzed the impact of BC on body adiposity of mice. To genetically dissect the roles of Bcmo1 and Bcdo2 in this process, we used wild-type and Bcmo1-/- mice for this study. In wild-type mice, BC was converted into retinoids. In contrast, Bcmo1-/- mice showed increased expression of Bcdo2 in adipocytes and β-10′-apocarotenol accumulated as the major BC derivative. In wild-type mice, BC significantly reduced body adiposity (by 28%), leptinemia and adipocyte size. Genome wide microarray analysis of inguinal white adipose tissue revealed a generalized decrease of mRNA expression of peroxisome proliferator-activated receptor γ (PPARγ) target genes. Consistently, the expression of this key transcription factor for lipogenesis was significantly reduced both on the mRNA and protein levels. Despite β-10′-apocarotenoid production, this effect of BC was absent in Bcmo1-/- mice, demonstrating that it was dependent on the Bcmo1-mediated production of retinoids. Our study evidences an important role of BC for the control of body adiposity in mice and identifies Bcmo1 as critical molecular player for the regulation of PPARγ activity in adipocyte

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

Fysiologische regulatie van de energiebalans - Een literatuuroverzicht

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.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.VWS-VG