The Effect of Downsizing Packages of Energy-Dense, Nutrient-Poor Snacks and Drinks on Consumption, Intentions, and Perceptions—A Scoping Review

The single-serve packaging of discretionary foods is becoming increasingly popular, but evidence is limited on whether smaller package sizes can reduce food intake. The aim of this scoping review is to assess the effect of reducing the package size of energy-dense, nutrient-poor (EDNP) snacks and drinks on consumption, intentions, and perception, and to examine the effects of potential moderators or mediators. The search was conducted in six selected databases and grey literature sources, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses for the scoping review process (PRISMA-ScR) guidelines. After screening 5562 articles, 30 articles comprising 47 intervention studies were included. Twelve of 15 studies found a significant effect in lowering the actual or intended consumption when a single smaller package was offered compared with a single larger package. When the total serving size was held constant between varying package conditions, such as a multipack, single package, or unpackaged, the results on the actual and intended consumption were inconsistent and varied according to the presence of moderators. Overall, these findings suggest that an overall reduction in the size of a single package is a more promising strategy than providing multipacks to reduce consumption. Changes to the current food environment to promote single smaller packages of EDNP snacks and drinks are necessary to support the better selection of appropriate portion sizes and reduce consumption.

Reducing Methylglyoxal Rescues Obesity Related Phenotypes and Lifespan in a Leptin Receptor Deficient Mouse Model

Obesity remains one of the leading risk factors for aging and age-related diseases such as Alzheimer’s and type II diabetes, and effects 40% of the US population. The occurrence of obesity has been closely tied to an increase in sugar consumption with chronic hyperglycemia enhancing glycolysis. One of the byproducts of glycolysis is methylglyoxal (MGO), a reactive precursor for advanced glycation end-products (AGEs), which drives type II diabetes and its complications. We hypothesize that an MGO-derived AGE, MG-H1, affects hypothalamic regulation of food consumption and metabolism parallel to the leptin pathway in mice fed a high carbohydrate diet. Exogenous supplementation of MG-H1 increased food consumption rates and weight gain. Conversely, glycation byproduct lowering compounds (GLY-LOW), a customized chemical cocktail that blocks the production of MGO, rescued over-feeding phenotypes in wild-type mice. Furthermore, GLY-LOW treatment in a leptin receptor deficient mouse model rescued weight gain, diabetic phenotypes and lifespan. RNA sequencing of the hypothalamus of leptin receptor deficient mice treated with GLY-LOW showed significant downregulation of Rax, a gene responsible for tanycyte differentiation, and several genes involved in feeding and aging. We propose that specific cells in the hypothalamus both make and respond to MG-H1. We will also discuss evidence for the potential of GLY-LOW as a new class of therapeutics that reduce the effects of glycation to reduce food intake and slow aging.

An essential role for a discrete parasubthalamic nucleus subpopulation in appetite suppression

Food intake behavior is regulated by a network of appetite-inducing and appetite-suppressing neuronal populations throughout the brain. The parasubthalamic nucleus (PSTN), a relatively unexplored population of neurons in the posterior hypothalamus, has been hypothesized to regulate appetite due to its connectivity with other anorexigenic neuronal populations and because these neurons express Fos, a marker of neuronal activation, following a meal. However, the individual cell types that make up the PSTN are not well characterized, nor are their functional roles in food intake behavior. Here we identify and distinguish between two discrete PSTN subpopulations, those that express tachykinin-1 (PSTNTac1 neurons) and those that express corticotropin-releasing hormone (PSTNCRH neurons), and use a panel of genetically encoded tools in mice to show that PSTNTac1 neurons play an essential role in appetite suppression. Both subpopulations increase activity following a meal and in response to administration of the anorexigenic hormones amylin, cholecystokinin (CCK), and peptide YY (PYY). Interestingly, chemogenetic inhibition of PSTNTac1, but not PSTNCRH neurons, reduces the appetite-suppressing effects of these hormones. Consistently, optogenetic and chemogenetic stimulation of PSTNTac1 neurons, but not PSTNCRH neurons, is sufficient to reduce food intake in hungry mice. PSTNTac1 and PSTNCRH neurons project to distinct downstream brain regions, and stimulation of PSTNTac1 projections to individual anorexigenic populations reduces food consumption. Taken together, these results reveal the functional properties and projection patterns of distinct PSTN cell types and demonstrate an essential, anorexigenic role for PSTNTac1 neurons in the hormonal and central regulation of appetite.

Robust Reductions of Body Weight and Food Intake by an Oxytocin Analog in Rats

Background: Oxytocin is a hypothalamic neuropeptide that participates in the network of appetite regulation. Recently the oxytocin signaling pathway has emerged as an attractive target for treating obesity. However, the short half-life limits its development as a clinical therapeutic. Here we provide results from testing a long-lasting, potent and selective oxytocin analog ASK1476 on its efficacy to reduce food intake and body weight in comparison to the native oxytocin peptide.Methods: ASK1476 features two specific amino acid substitutions in positions 7 and 8 combined with a short polyethylene glycol spacer. Short time dose escalation experiments testing increasing doses of 3 days each were performed in diet-induced overweight (DIO) male rats assessing effects on body weight as well as changes in food intake. Furthermore, DIO rats were tested for changes in body weight, food intake, temperature, and locomotor activity over 28 days of treatment (oxytocin, ASK1476, or vehicle).Results: In dose escalation experiments, significant reductions in food intake relative to baseline were detected beginning with doses of 15 nmol/kg ASK1476 (−15.2 ± 2.3 kcal/d, p = 0.0017) and 20 nmol/kg oxytocin (−11.2.9 ± 2.4 kcal/d, p = 0.0106) with corresponding significant changes in body weight (ASK1476: −5.2 ± 0.8 g, p = 0.0016; oxytocin: −2.6 ± 0.7 g, p = 0.0326). In long-term experiments, there was no difference on body weight change between 120 nmol/kg/d ASK1476 (−71.4 ± 34.2 g, p = 0.039) and 600 nmol/kg/d oxytocin (−91.8 ± 32.2 g, p = 0.035) relative to vehicle (706.9 ± 28.3 g), indicating a stronger dose response for ASK1476. Likewise, both ASK1476 and oxytocin at these doses resulted in similar reductions in 28-day cumulative food intake (ASK1476: −562.7 ± 115.0 kcal, p = 0.0001; oxytocin: −557.1 ± 101.3 kcal, p = 0.0001) relative to vehicle treatment (2716 ± 75.4 kcal), while no effects were detected on locomotor activity or body temperature.Conclusion: This study provides proof-of-concept data demonstrating an oxytocin analog with extended in vivo stability and improved potency to reduce food intake and body weight in DIO animals which could mark a new avenue in anti-obesity drug interventions.

Mechanisms in Endocrinology: The physiology of neuronostatin

In 2008, the first evidence of a new hormone called neuronostatin was published. The hormone was discovered using a bioinformatic method and found to originate from the same preprohormone as somatostatin. This small peptide hormone of 13 amino acids and a C-terminal amidation was soon found to exert pleiotropic physiological effects. In animal studies, neuronostatin has been shown to reduce food intake, and delay gastric emptying and gastrointestinal transit. Furthermore, neuronostatin has been shown to affect glucose metabolism by increasing glucagon secretion during situations when glucose concentrations are low. Additionally, neuronostatin has been shown to affect neural tissue and cardiomyocytes by suppressing cardiac contractility. The effects of neuronostatin have not yet been delineated in humans, but if the effects found in animal studies translate to humans it could position neuronostatin as a promising target in the treatment of obesity, hypertension and diabetes. In this review, we describe the discovery of neuronostatin and the current understanding of its physiological role and potential therapeutic applicability.

Development and evaluation of a virtual reality puzzle game to decrease food intake (Preprint)

BACKGROUND Virtual Reality (VR) has gained popularity in daily life and VR food cues seem to elicit food cravings as similar to real food cues. However, little is known about the impact of VR food cues on actual food intake. OBJECTIVE In Real-Life (RL), exposure to food cues in a situation where the desire to eat food interferes with the completion of a food-related task reduces the subsequent food intake (i.e., the pre-exposure effect). In this study, we examine on the one hand whether the pre-exposure effect could be replicated in RL and on the other hand whether this effect could be extended to VR contexts. METHODS The current research employed a 2 (Stimulus Type: Food vs. Nonfood) × 2 (Mode: VR vs. RL) between-subject design (n = 175). Participants were randomly assigned to one of the four conditions. RESULTS We found the main effect of mode on food intake with a higher food intake after both VR conditions than after RL conditions (p = .020). Also, among female participants, we found that exposure to both food cues (i.e., VR and RL) resulted in lower food intake than exposure to both nonfood cues (p = .048). In contrast, this effect was not observed among male participants (p = .336). Additionally, VR and RL cues generated similar emotional and behavioral responses (e.g., arousal and game difficulty). CONCLUSIONS We were unable to replicate the exposure effect in our complete sample. Sub-group analyses, however, showed that for women exposure to food cues (either in VR or RL) did reduce food intake, indicating that a VR pre-exposure procedure may effectively be applied exclusively for women.

Anorexia and fat aversion induced by vertical sleeve gastrectomy is attenuated in neurotensin receptor 1 deficient mice

Neurotensin (NT) is an anorexic gut hormone and neuropeptide that increases in circulation following bariatric surgery in humans and rodents. We sought to determine the contribution of NT to the metabolic efficacy of vertical sleeve gastrectomy (VSG). To explore a potential mechanistic role of NT in VSG, we performed sham or VSG surgeries in diet-induced obese neurotensin receptor 1 (NTSR1) wildtype (wt) and knockout (ko) mice and compared their weight and fat mass loss, glucose tolerance, food intake, and food preference after surgery. NTSR1 ko mice had reduced initial anorexia and body fat loss. Additionally, NTSR1 ko mice had an attenuated reduction in fat preference following VSG. Results from this study suggest that NTSR1 signaling contributes to the potent effect of VSG to initially reduce food intake following VSG surgeries and potentially also on the effects on macronutrient selection induced by VSG. However, maintenance of long-term weight loss after VSG requires signals in addition to NT.

Activation of the hypothalamic–pituitary–adrenal axis by exogenous and endogenous GDF15

An acute increase in the circulating concentration of glucocorticoid hormones is essential for the survival of severe somatic stresses. Circulating concentrations of GDF15, a hormone that acts in the brain to reduce food intake, are frequently elevated in stressful states. We now report that GDF15 potently activates the hypothalamic–pituitary–adrenal (HPA) axis in mice and rats. A blocking antibody to the GDNF-family receptor α-like receptor completely prevented the corticosterone response to GDF15 administration. In wild-type mice exposed to a range of stressful stimuli, circulating levels of both corticosterone and GDF15 rose acutely. In the case of Escherichia coli or lipopolysaccharide injections, the vigorous proinflammatory cytokine response elicited was sufficient to produce a near-maximal HPA response, regardless of the presence or absence of GDF15. In contrast, the activation of the HPA axis seen in wild-type mice in response to the administration of genotoxic or endoplasmic reticulum toxins, which do not provoke a marked rise in cytokines, was absent in Gdf15−/− mice. In conclusion, consistent with its proposed role as a sentinel hormone, endogenous GDF15 is required for the activation of the protective HPA response to toxins that do not induce a substantial cytokine response. In the context of efforts to develop GDF15 as an antiobesity therapeutic, these findings identify a biomarker of target engagement and a previously unrecognized pharmacodynamic effect, which will require monitoring in human studies.

EXPRESS: How Communications that Portray Unhealthy Food Consumption Reduce Food Intake Among Dieters

Both regulatory agencies and nonprofit organizations seek to understand how different tactics and appeals contained in food and public health advertisements might influence the food intake of an increasingly dieting-concerned population. This article addresses this important issue by examining how consumers who are concerned with their diets react to rich images of unhealthy food consumption. Results of two experiments show that exposure to food advertisements containing unhealthy food consumption imagery reduces food intake among consumers chronically concerned with dieting, whereas a third experiment shows a similar decrease in intended consumption when a public health advertisement portrays the consumption of unhealthy food. These findings in turn offer guidelines for maximizing the effectiveness of messages that attempt to promote healthy eating habits. Additionally, this research provides theoretical contributions to the self-control and mental imagery research domains which have public policy implications for regulatory agencies and nonprofit organizations.

Preclinical Weight Loss Efficacy of AM833 in Combination With Semaglutide in Rodent Models of Obesity

Weight management pharmacotherapies seldom induce body weight loss that is comparable to that produced by bariatric surgery. In this regard, combination therapies targeting multiple signaling pathways that regulate energy balance may provide a means to achieve greater weight loss efficacy while also allowing the use of lower doses of each drug, and thus mitigating potential gastrointestinal tolerability issues commonly observed with current therapeutics for weight management. Amylin and GLP-1 are peptide hormones that regulate appetite. Upon ingestion of a meal, amylin is co-secreted with insulin from pancreatic beta-cells, while GLP-1 is secreted from enteroendocrine cells in the intestine. Both native peptides have a short half-life and reduce food intake, delay gastric emptying and decrease glucagon levels. Amylin and GLP-1 analogues have been developed for the treatment of diabetes, as well as weight management. The long-acting once-weekly GLP-1 analogue, semaglutide is approved for the treatment of type 2 diabetes and is in clinical development for weight management. AM833 (NNC0174-0833) is a long-acting, once-weekly human amylin analogue that is also in clinical development for weight management. Here, we present the combined effect of AM833 and semaglutide on weight loss in rodent models of obesity. Diet-induced obese (DIO) rats and mice on a high energy diet were dosed subcutaneously once-daily for 24 or 28 days with sub-maximal doses of AM833, semaglutide or two modes of combination treatments. The first combination mode consisted of concurrent co-dosing of both drugs, while the second entailed add-on of AM833 after one week of treatment with semaglutide. Body weight and food intake were measured daily. Body composition was assessed by magnetic resonance scan pre- and post-treatment. In the DIO rat, both concurrent (-13.1% ± 0.7%) and add-on (-12.8% ± 1.2%) treatment modes induced equivalent weight loss that was greater than each monotherapy (-6.3% ± 0.7%, 2 nmol/kg semaglutide and -5.8% ± 0.9%, 2 nmol/kg AM833) relative to initial body weights. Both combination groups achieved normalization of body weight to that of lean age-matched control rats. Reductions in cumulative food intake corresponded with the extent of weight loss. In the DIO mouse, weight loss in the combination groups was not significantly different (-9.6% ± 1.5%, concurrent vs. -11.5% ± 1.2%, add-on) but was greater than that observed in each monotherapy group (-1.9% ±1.2%, 1 nmol/kg semaglutide and +1.5% ± 2.2%, 10 nmol/kg AM833). In the DIO mouse, body weight did not normalize to match that of lean controls with combination treatment. In both rodent models, combination therapy at submaximal doses of AM833 and semaglutide achieved significantly greater weight loss compared to the monotherapy groups highlighting the potential of this combination for further clinical development.