Nutrient stimulation of enteroendocrine L cells induces the release of the incretin and satiating peptide glucagon-like 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 long-term 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) 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. We 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. GLP-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. Collectively, our data show that DMH GLP-1R signaling plays a key role for BAT thermogenesis and adiposity.

The gut-brain hormone glucagon-like peptide-1 (GLP-1) has received immense attention over the last couple of decades for its widespread metabolic effects. Notably, intestinal GLP-1 has been recognized as an endogenous satiation signal. Yet, the underlying mechanisms and the pathophysiological relevance of intestinal GLP-1 in obesity remain unclear. This review first recapitulates early findings indicating that intestinal GLP-1 is an endogenous satiation signal, whose eating effects are primarily mediated by vagal afferents. Second, on the basis of recent findings challenging a paracrine action of intestinal GLP-1, a new model for the mediation of GLP-1 effects on eating by two discrete vagal afferent subsets will be proposed. The central mechanisms processing the vagal anorexigenic signals need however to be further delineated. Finally, the idea that intestinal GLP-1 secretion and/or effects on eating are altered in obesity and play a pathophysiological role in the development of obesity will be discussed. In summary, despite the successful therapeutic use of GLP-1 receptor agonists as anti-obesity drugs, the eating effects of intestinal GLP-1 still remain to be elucidated. Specifically, the findings presented here call for a further evaluation of the vago-central neuronal substrates activated by intestinal GLP-1 and for further investigation of its pathophysiological role in obesity.

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.

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.