Nutrient stimulation of enteroendocrine L cells induces the release of the incretin and satiating peptide glucagonlike peptide 1 (GLP-1). The vagus nerve innervates visceral organs and may contribute to the mediation of gut-derived GLP-1's effects on food intake, energy homeostasis, and glycemic control. To test the hypothesis that vagal afferent neuron (VAN) GLP-1 receptors (GLP-1Rs) are necessary for these effects of endogenous GLP-1, we established a novel bilateral nodose ganglia injection technique to deliver a lentiviral vector and to knock down VAN GLP-1Rs in male Sprague Dawley rats. We found that a full expression of VAN GLP-1Rs is not necessary for the maintenance of longterm energy balance in normal eating conditions. VAN GLP-1R knockdown (kd) did, however, increase meal size and accelerated gastric emptying. Moreover, postmeal glycemia was elevated and insulin release was blunted in GLP-1R kd rats, suggesting that VAN GLP-1Rs are physiological contributors to the neuroincretin effect after a meal. Collectively, our results highlight a crucial role for the VANs in mediating the effects of endogenous GLP-1 on food intake and glycemia and may promote the further development of GLP-1-based therapies.Glucagon-like peptide 1 (GLP-1) is an incretin and satiating hormone that has provided new tools for the pharmacotherapy of obesity and diabetes (1,2). Yet, despite the clinical effectiveness of GLP-1-based drugs in ameliorating the symptoms of type 2 diabetes, the role of endogenous GLP-1 in the control of energy intake and glucose homeostasis is not fully understood. Vagal afferent neurons (VANs) express GLP-1 receptors (GLP-1Rs) (3,4) and terminate in the lamina propria of the intestinal mucosa as well as in the wall of the hepatic portal vein (HPV) (5). VANs may therefore relay the gut GLP-1-derived signals to the brain and, hence, mediate satiating and glucoregulatory responses. Previous studies using lesioning approaches have implicated the vagus nerve in the effects of peripherally administered GLP-1 on food intake and glycemia (reviewed in 6,7). In more recent studies, sudiaphragmatic vagal deafferentation (SDA) in rats clearly attenuated the acute eating-inhibitory effect of intraperitoneally (IP) infused GLP-1 (8) and exendin-4 (Ex-4), a GLP-1R agonist (9). Moreover, unlike Sham-operated rats, SDA rats failed to show a GLP-1R-mediated incretin response (10). Based on these findings, it is reasonable to hypothesize that endogenous gut-derived GLP-1 could activate GLP-1Rs on VANs in a paracrine-like fashion to reduce food intake, limit gastric emptying, and trigger a neural component of the incretin effect. Disruption of this endogenous GLP-1 signaling mechanism in the VANs due to genetic or environmental factors may contribute to the pathophysiology of obesity and diabetes. Hence, we examined the physiological role of in the control of food intake and regulation of glucose homeostasis by generating a specific knockdown (kd) of VAN GLP-1R expression in rats. Our approach is based on the delivery of a...

In this national Canadian cohort, vitamin D levels <75 nmol/L were common, particularly among non-white and obese individuals, and in winter and spring. Vitamin D intake through diet and supplementation and maintenance of normal weight are key modifiable factors for enhancing vitamin D status and thus potentially influencing susceptibility to common chronic diseases.

Sociodemographic differences in dietary consumption were observed in different populations. The current study aimed to identify sociodemographic and lifestyle determinants of diet quality and to investigate the differences in diet quality between the three main language regions of Switzerland. Using data of the Swiss National Nutrition Survey menuCH (n = 2057), two diet quality scores—Alternate Healthy Eating Index and Mediterranean Diet Score—were computed. Linear regression models were used to investigate the determinants of diet quality and chi-square tests were used to test for differences in single score components between language regions. Significantly higher diet quality scores were observed for individuals who were female, older, normal weight, non-Swiss, with tertiary education or moderate-to-high physical activity level. Additionally, residents of the French- and Italian-speaking parts of Switzerland scored higher than residents of the German-speaking region. More specifically, the higher diet quality observed in the French- and Italian-speaking regions was mediated by higher scores in the components of alcohol, dairy products, fat, fish, sugar-sweetened beverages and whole grains. The present results may help to better characterize population groups requiring specific dietary recommendations, enabling public health authorities to develop targeted interventions.

From a public health perspective, determinants of diets are crucial to identify, but they remain unclear in Switzerland. Hence, we sought to define current dietary patterns and their sociodemographic and lifestyle determinants using the national nutrition survey menuCH (2014–2015, n = 2057). First, we applied multiple factorial analysis and hierarchical clustering on the energy-standardised daily consumption of 17 food categories. Four dietary patterns were identified (“Swiss traditional”: high intakes of dairy products and chocolate, n = 744; “Western 1”: soft drinks and meat, n = 383; “Western 2”: alcohol, meat and starchy, n = 444; and “Prudent”: n = 486). Second, we used multinomial logistic regression to examine the determinants of the four dietary patterns: ten sociodemographic or lifestyle factors (sex, age, body mass index, language region, nationality, marital status, income, physical activity, smoking status, and being on a weight-loss diet) were significantly associated with the dietary patterns. Notably, belonging to the French- and Italian-speaking regions of Switzerland increased the odds of following a “Prudent” diet (Odds ratio [95% confidence interval]: 1.92 [1.45–2.53] and 1.68 [0.98–2.90], respectively) compared to the German-speaking regions. Our findings highlight the influence of sociodemographic and lifestyle parameters on diet and the particularities of the language regions of Switzerland. These results provide the basis for public health interventions targeted for population subgroups.

Prevalence and health consequences of obesity differ between men and women. Yet, most preclinical studies investigating the etiology of obesity have, to date, been conducted in male rodents. Notably, diet is a major determinant of obesity, but sex differences in rodent models of diet-induced obesity, and the mechanisms that underlie such differences, are still understudied. Here, we aim to determine whether time course and characteristics of diet-induced obesity differ between sexes in rats and mice, and to investigate the potential causes of the observed divergence. To achieve this, we offered the most commonly tested rodents of both sexes, SD rats and C57BL/6 mice, a free choice of 60 % high-fat diet (HFD) and regular chow; body weight, food intake, fat mass, brown adipose responses, locomotor activity and glucose tolerance were assessed in a similar manner in both species. Our results indicate that overall diet-induced hyperphagia is greater in males but that females display a higher preference for the HFD, irrespective of species. Female rats, compared to males, showed a delay in diet-induced weight gain and less metabolic complications. Although male rats increased brown adipose tissue thermogenesis in response to the HFD challenge, this was not sufficient to counteract increased adiposity. In contrast to rats, female and male mice presented with a dramatic adiposity and impaired glucose tolerance, and a decreased energy expenditure. Female mice showed a 5-fold increase in visceral fat, compared to 2-fold increase seen in male mice. Overall, we found that male and female rodents responded very differently to HFD challenge, and engaged different compensatory energy expenditure mechanisms. In addition, these sex differences are divergent in rats and mice. We conclude that SD rats have a better face validity for the lower prevalence of overweight in women, while C57BL/6 mice may better model the increased prevalence of morbid obesity in women.

ObjectiveGlucagon-like peptide-1 (GLP-1) neurons in the hindbrain densely innervate the dorsomedial hypothalamus (DMH), a nucleus strongly implicated in body weight regulation and the sympathetic control of brown adipose tissue (BAT) thermogenesis. Therefore, DMH GLP-1 receptors (GLP-1R) are well placed to regulate energy balance by controlling sympathetic outflow and BAT function.MethodsWe investigate this possibility in adult male rats by using direct administration of GLP-1 (0.5 ug) into the DMH, knocking down DMH GLP-1R mRNA with viral-mediated RNA interference, and by examining the neurochemical phenotype of GLP-1R expressing cells in the DMH using in situ hybridization.ResultsGLP-1 administered into the DMH increased BAT thermogenesis and hepatic triglyceride (TG) mobilization. On the other hand, Glp1r knockdown (KD) in the DMH increased body weight gain and adiposity, with a concomitant reduction in energy expenditure (EE), BAT temperature, and uncoupling protein 1 (UCP1) expression. Moreover, DMH Glp1r KD induced hepatic steatosis, increased plasma TG, and elevated liver specific de-novo lipogenesis, effects that collectively contributed to insulin resistance. Interestingly, DMH Glp1r KD increased neuropeptide Y (NPY) mRNA expression in the DMH. GLP-1R mRNA in the DMH, however, was found in GABAergic not NPY neurons, consistent with a GLP-1R-dependent inhibition of NPY neurons that is mediated by local GABAergic neurons. Finally, DMH Glp1r KD attenuated the anorexigenic effects of the GLP-1R agonist exendin-4, highlighting an important role of DMH GLP-1R signaling in GLP-1-based therapies.ConclusionsCollectively, our data show that DMH GLP-1R signaling plays a key role for BAT thermogenesis and adiposity.

The first stable gold(III) formate and experimental evidence for its β-hydride elimination are described. A catalytic dehydrogenation of formic acid together with mechanistic studies shed light on potential pathways operating in fundamental gold-catalyzed transformations.

The small intestine is the main organ involved in the digestion and absorption of nutrients. It is in an ideal position to sense the availability of energy in the lumen in addition to its absorptive function. Consumption of a high-fat diet (HFD) influences the metabolic characteristics of the small intestine. Therefore, to better understand the metabolic features of the small intestine and their changes in response to dietary fat, we characterized the metabolism of duodenal, jejunal, and hepatic cell lines and assessed the metabolic changes in the enterocytes and the liver after short-term (3 days) or medium-term (14 days) HFD feeding in mice. Experiments with immortalized enterocytes indicated a higher glycolytic capacity in the duodenal cell line compared to the other two cell lines, whereas the jejunal cell line exhibited a high oxidative metabolism. Short-term HFD feeding induced changes in the expression of glucose and lipid metabolism-related genes in the duodenum and the jejunum of mice, but not in the liver. When focusing on fatty acid oxidation both, short- and medium-term HFD feeding induced an upregulation of 3-hydroxy-3-methylglutaryl-coenzyme A, the key enzyme of ketogenesis, at the protein level in the intestinal epithelial cells, but not in the liver. These results suggest that HFD feeding induces an early adaptation of the small intestine rather than the liver in response to a substantial fat load. This highlights the importance of the small intestine in the adaptation of the body to the metabolic changes induced by HFD exposure. J. Cell. Physiol. 232: 167-175, 2017. © 2016 Wiley Periodicals, Inc.