Human Appetite Research Articles

Association of Geriatric Depression with Biosocial Factors and Malnutrition in Rural Areas of District Gautam Budh Nagar, Uttar Pradesh: A Community-Based Study

Background: Aging mainly affects human appetite, food intake, and body weight. Physiological and psychopharmacological pathways demonstrate variations in hunger. Bodily signs characterize Elderly Depression, altered eating and sleeping patterns, cognitive impairments, and low mood. Objectives: To study the prevalence of Depression and Malnutrition in the geriatric population in the rural community and to examine the association between them among the study population. Methods: A community-based cross-sectional study was conducted in the rural areas of district Gautam Budh Nagar among geriatric population using a pre-designed pretested semi-structured questionnaire. Results: In the study, the prevalence of Depression among the study participants was found to be 155(41.2%) and malnutrition was found to be in 67 (17.8 %). Among bio social characters Age (p-value-0.000), gender (p-value-0.012), marital status (p-value-0.026), physical activity (p-value-0.004), and Malnutrition (p-value-0.000) found to be significantly associated with Depression among elderly. On multiple logistic regression, physical activity [aOR 23.6; 95% CI: 11.4-48.8] and Malnutrition or its risk [aOR 0.272; 95% CI: 0.130-0.569] were significantly associated with Geriatric Depression. Conclusions: Depression is recognized to have a significant impact on nutritional health in the elderly and is a major factor in weight loss.

7141 Disruption of Transient Receptor Potential Channel 5 Causes Obesity and Maladaptive Behavior

Abstract Disclosure: Y. Li: None. T. Cacciottolo: None. I.S. Farooqi: None. Y. Xu: None. The global surge in obesity over recent decades poses formidable challenges to public health and economic well-being. Transient Receptor Potential Channel 5 (TRPC5) emerges as a pivotal membrane-spanning cation channel implicated in energy homeostasis, pain modulation, and fear responses. Here, we identified microdeletions on chromosome Xq23 disrupting TRPC5 in boys with food-seeking, obesity, anxiety and autism. Significantly, these microdeletions were inherited from mothers grappling with a constellation of health issues, including obesity and anxiety, suggesting a potential intergenerational aspect to TRPC5-related conditions. We examined approximately 450,000 individuals with exome sequence data from the UK Biobank and found that the TRPC5 gene is the most strongly associated X-linked gene for human body mass index. Moreover, we identified 7 rare TRPC5 variants in patients with severe obesity underscores the potential role of TRPC5 in shaping the obesity phenotype. Functional experiments with HEK293 cells demonstrated that these variants led to a loss of Trpc5 function. Knock-in male mice harboring a human loss-of-function (LOF) TRPC5 variant developed obesity, anxiety, reduced social exploratory behavior and increased aggression; female mice homozygous for the same variant showed similar deficits with reduced severity. We found approximately 91% proopiomelanocortin (Pomc) neurons in arcuate nucleus of the hypothalamus (ARH) express Trpc5 in wild-type male mice. Utilizing the TRPC5 agonist benzothiadiazide derivative (BTD), we found that BTD (i.p., 10 mg/kg) reduced food intake and increased c-Fos expression in Pomc neurons in wild-type mice compared to the vehicle injection group. Importantly, the activation of Trpc5 using BTD did not induce toxicity or aversive effects. Importantly, chemogenetic inactivation using designer receptor exclusively activated by designer drugs (DREADD) of hM4Di-expressing Pomc neurons with clozapine N-oxide (CNO; i.p., 1 mg/kg) effectively blocked BTD-induced anorexia and c-Fos expression in Pomc neurons. Furthermore, we found that BTD-induced anorexia and c-Fos expression in Pomc neurons were blocked in mice with a LOF TRPC5 variant. This suggesting that the effects of BTD on food intake are mediated through Trpc5 in Pomc neurons. In conclusion, our study provides compelling evidence for the involvement of TRPC5 in the intricate regulation of human appetite, body weight, and maladaptive behaviors. Our findings suggest that melanocortin receptor agonists might be effective in treating severe obesity in individuals carrying TRPC5 variants. We suggest that TRPC5 should be included in diagnostic gene panels for severe childhood-onset obesity. Presentation: 6/1/2024

The Impact of Exercise Intensity and Sex on Endogenous Ghrelin Levels and Appetite in Healthy Humans.

Ghrelin circulates in acylated (AG) and deacylated (DAG) forms, which are known to affect appetite. Although acute exercise has been shown to modulate ghrelin levels, data on the impact of exercise intensity on AG and DAG levels and their effects on appetite are sparse and primarily limited to males. To investigate the effect of exercise intensity and sex on ghrelin levels and appetite in untrained humans. Eight males (age: 43.1 ± 10.9 years; body mass index [BMI]: 22.2 ± 1.7 kg/m2; peak oxygen consumption [VO2peak]: 36.3 ± 6.4 mL/kg/min) and 6 females (age: 32.2 ± 11.1 years; BMI: 22.7 ± 1.0 kg/m2; VO2peak: 29.2 ± 4.0 mL/kg/min) completed a maximal graded cycle ergometer lactate threshold (LT)/VO2peak test. These data were used to determine the exercise intensity on 3 subsequent randomized control or calorically matched cycle exercise bouts: (1) CON, no exercise; (2) MOD, the power output at LT; (3) HIGH, the power output associated with 75% of the difference between LT and VO2peak. Perception of appetite was analyzed using visual analog scales. Females had higher levels of total ghrelin (TG) (P = .03) and DAG (P = .01) at baseline than males. Both groups exhibited reduced DAG levels in HIGH compared with MOD and CON (P < .0001-.004); however, only females had significantly reduced AG in HIGH (P < .0001). Hunger scores were higher in MOD than in CON (P < .01). High-intensity may be superior to moderate-intensity exercise for reducing ghrelin levels and modifying hunger, and sex may impact this response.

Christian Higher Education at Secular Universities: A Multiple-Case Study of Christian Study Centers and Institutes for Catholic Thought

For over 50 years, a group of Christians has cultivated a movement to revitalize Christian education at secular universities. These leaders formed centers for Christian thought (CCT) to reengage the Christian faith with the intellectual life (and vice-versa) and work with students, staff, and faculty within American universities. At present, there are at least 41 CCT in the USA, but little empirical work has been done to explore this type of Christian education. In this paper, we used a collective case study of five established CCT to answer the following research question: What are the distinctive features of Christian study centers and institutes for Catholic thought, and what is the nature of Christian education they offer? Each center we studied exhibited characteristics unique to its institutional context and yet shared some key educational elements with other centers. In sum, CCT used hospitality and intellectual fellowship to engage the riches of the Christian intellectual tradition to satiate the human appetite to live an integrated life. The center staff believed that living the integrated life would strengthen the global church and thereby benefit the university and society. Although CCT are distinct from Christian colleges and universities, opportunities exist for mutual learning between them that could help perpetuate the Christian intellectual tradition. For example, CCT could benefit from the faith integration conversations happening on Christian campuses, who could, in turn, learn from the holistic approaches of CCT and benefit from hiring faculty who were involved with a center as graduate students.

Pre-prandial plasma liver-expressed antimicrobial peptide 2 (LEAP2) concentration in humans is inversely associated with hunger sensation in a ghrelin independent manner.

The liver-expressed antimicrobial peptide 2 (LEAP2) is a newly recognized peptide hormone that acts via the growth hormone secretagogue receptor (GHSR) blunting the effects of ghrelin and displaying ghrelin-independent actions. Since the implications of LEAP2 are beginning to be elucidated, we investigated if plasma LEAP2 concentration varies with feeding status or sex and whether it is associated with glucose metabolism and appetite sensations. We performed a single test meal study, in which plasma concentrations of LEAP2, ghrelin, insulin and glucose as well as visual analogue scales for hunger, desire to eat, prospective food consumption, fullness were assessed before and 60min after breakfast in 44 participants (n = 21 females) with normal weight (NW) or overweight/obesity (OW/OB). Pre-prandial plasma LEAP2 concentration was ~ 1.6-fold higher whereas ghrelin was ~ 2.0-fold lower in individuals with OW/OB (p < 0.001) independently of sex. After adjusting for body mass index (BMI) and sex, pre-prandial plasma LEAP2 concentration displayed a direct relationship with BMI (β: 0.09; 95%CI: 0.05, 0.13; p < 0.001), fat mass (β: 0.05; 95%CI: 0.01, 0.09; p = 0.010) and glycemia (β: 0.24; 95%CI: 0.05, 0.43; p = 0.021), whereas plasma ghrelin concentration displayed an inverse relationship with BMI and fat mass but not with glycemia. Postprandial plasma LEAP2 concentration increased ~ 58% in females with OW/OB (p = 0.045) but not in females with NW or in males. Pre-prandial plasma LEAP2 concentration displayed an inverse relationship with hunger score (β: -11.16; 95% CI: -18.52, -3.79; p = 0.004), in a BMI-, sex- and ghrelin-independent manner. LEAP2 emerges as a key hormone implicated in the regulation of metabolism and appetite in humans. The study was retrospectively registered in clinicaltrials.gov (April 2023). gov Identifier: NCT05815641.

Hypobaric hypoxia induces iron mobilization from liver and spleen and increases serum iron via activation of ghrelin/GHSR1a/MAPK signalling pathway in mice

Hypobaric hypoxia (HH) exposure affects appetite and serum iron levels in both humans and animals. Thus, whether appetite-regulating ghrelin is involved in iron regulation under HH needs to be elucidated. In vivo, C57BL/6J mice were placed in a hypobaric chamber to establish a 6000-m-high altitude exposure animal model. In vitro, mouse primary hepatocytes and peritoneal macrophages were exposed to hypoxia (1% O2) to examine the effects of ghrelin on iron-regulating proteins. HH obviously reduced the body weight of mice and significantly increased the levels of erythrocytes, and also significantly enhanced the levels of serum iron and plasma ghrelin. However, iron content in the liver and spleen was decreased, while ferroportin (Fpn) expression was increased. Moreover, ghrelin significantly induced Fpn and pERK expression in both hepatocytes and macrophages under hypoxia, which were reversed by pretreatment with growth hormone secretagogue receptor 1a (GHSR1a) antagonist or pERK inhibitor. Our findings indicated that HH leads to decreased appetite and insufficient dietary intake, which may negatively regulate the levels of ghrelin. Furthermore, GHSR1a/ERK signalling pathway is further activated to upregulate the expression of Fpn, and then promoting iron mobilization both in the liver/hepatocytes and spleen/macrophages in mice. Thus, these results revealed that ghrelin may be a potential iron regulatory hormone, and raised the possibility of ghrelin as a promising therapeutic target against iron disorders under HH.

What can functional brain imaging teach us about remission of type 2 diabetes?

With a paradigm shift in attitudes to type 2 diabetes (T2D), "weight-loss responsive" diabetes is now thought of as a curable disease state. As a result, national programmes are being orchestrated to induce T2D remission soon after diagnosis with aggressive dietary interventions - such as very-low-calorie diets (VLCD). However, dietary interventions to achieve weight loss and diabetes remission lack the same long-term sustainability and cardiovascular risk reduction evidence as bariatric surgery. Improving our understanding of the neural implications of T2D that promote disadvantageous eating behaviours will enable prevention of disease as well as mitigation against a vicious cycle of metabolic dysfunction and associated cognitive complications. Here we summarise how functional MRI (fMRI) studies have helped to fashion our understanding of the neurobiology of human appetite and obesity. We explore how these neural correlates are affected by insulin resistance and T2D itself as well as its different treatment approaches. Finally, we comment on the need for more personalised approaches to maintaining metabolic health and how fMRI studies may inform this.

Obesity and thinness: insights from genetics.

Genetic disruption of key molecular components of the hypothalamic leptin-melanocortin pathway causes severe obesity in mice and humans. Physiological studies in people who carry these mutations have shown that the adipose tissue-derived hormone leptin primarily acts to defend against starvation. A lack of leptin causes an intense drive to eat and increases the rewarding properties of food, demonstrating that human appetite has a strong biological basis. Genetic studies in clinical- and population-based cohorts of people with obesity or thinness continue to provide new insights into the physiological mechanisms involved in weight regulation and identify molecular targets for weight loss therapy. This article is part of a discussion meeting issue 'Causes of obesity: theories, conjectures and evidence (Part II)'.

‘Like Skulls at Memphian Banquets’: The Mouth and Mortality in Byron’s Don Juan

This article examines the relationship between appetite, mortality, and laughter in Lord Byron’s Don Juan . While the vegetarian Percy Bysshe Shelley argued that human appetites could be directed away from cruelty and death, Byron presents appetite as both naturally carnivorous and inextricably linked to mortality. Furthermore, by examining the role of laughter in Don Juan ’s Canto II and Canto IX, I argue that the Byronic laugh is also mimetic of Death’s triumphant appetite: a response to the inescapable link between human appetite and Death as well as an imitation of Death’s role as the laughing archdevourer of life. However, in the latter part of my article, I argue that in the last canto of Don Juan , Byron tentatively theorizes a metaphysical appetite that may exist beyond Death and laughter. In so doing, Byron posits a utopian vision of appetite – a vision that, interrupted by the poet’s own death, remains unresolved.

Gut microbiota fermentation profiles of pre-digested mycoprotein (Quorn) using faecal batch cultures in vitro: a preliminary study

High-fibre diets are beneficial for many health outcomes via a wide range of mechanisms including gut microbiota fermentation-derived short-chain fatty acid (SCFAs) production. Mycoprotein (marketed as Quorn) is a food high in fibre (>6 g/100 g wet weight (ww)) and protein (13 g/100 g ww) which has been shown to have positive effects on glycemic control and appetite in humans. Nevertheless, the mechanisms underpinning this are poorly understood. Here, we investigate the changes in gut microbiota α- and β-diversity, pH and SCFAs production in faecal batch cultures supplemented with pre-digested mycoprotein (Quorn), soy, chicken and control (unsupplemented) using eight fresh stools from healthy donors. The results showed that pre-digested mycoprotein did not alter pH (p = .896), α- or β-diversity of the gut microbiota when compared to the control, soy, and chicken. Nevertheless, chicken led to a significant increase in total SCFAs post-24 h vs. control (+57.07 mmol/L, p = .01). In particular, propionate increased when compared to soy (+19.59 mmol/L, p = .03) and the control (+23.19 mmol/L, p < .01). No other differences in SCFAs were detected. In conclusion, pre-digested mycoprotein was not fermented in vitro by healthy gut microbiota in the settings of this experiment.

Inter-Day Variation in the Fasting Plasma Lipopolysaccharide Concentration in the Morning Is Associated with Inter-Day Variation in Appetite in Japanese Males: A Short-Term Cohort Study

Injection of lipopolysaccharide (LPS), a product of gut bacteria, into the blood increases blood triglycerides and cortisol, an appetite-stimulating hormone. Meanwhile, small amounts of LPS derived from gut bacteria are thought to enter the bloodstream from the gut in daily basis. This study aimed to investigate the effect of LPS influx on appetite or lipid metabolism in humans in everyday life. We measured the fasting plasma LPS concentration before breakfast and the corresponding days' appetite and fat-burning markers for 10 days in four Japanese males (28-31 years) and analyzed the correlation of their inter-day variation. The LPS concentration was negatively correlated with fullness, and positively correlated with the carbohydrate intake. Against our hypothesis, the LPS concentration was positively correlated with the fasting breath acetone concentration, a fat-burning marker. There was a positive correlation between the LPS concentration and fasting body mass index (BMI), but the inter-day variation in BMI was slight. The results suggest that the LPS influx in everyday life is at least associated with appetite in the day.

AgRP Neuron-Specific Ablation Represses Appetite, Energy Intake, and Somatic Growth in Larval Zebrafish

Neuronal circuits regulating appetite are dominated by arcuate nucleus neurons, which include appetite-promoting and -suppressing neurons that release the orexigenic neuropeptide agouti-related protein (AgRP) and anorexigenic neuropeptide pro-opiomelanocortin, respectively, to compete for melanocortin receptors to modulate feeding behavior. In this study, we expressed novel agrp promoters, including different lengths of the 5' flanking regions of the agrp gene (4749 bp) in the zebrafish genome. We used the agrp promoter to derive the enhanced green fluorescent protein (EGFP)-nitroreductase (NTR) fusion protein, allowing expression of the green fluorescence signal in the AgRP neurons. Then, we treated the transgenic zebrafish AgRP4.7NTR (Tg [agrp-EGFP-NTR]) with metronidazole to ablate the AgRP neurons in the larvae stage and observed a decline in their appetite and growth. The expression of most orexigenic and growth hormone/insulin-like growth factor axis genes decreased, whereas that of several anorexigenic genes increased. Our findings demonstrate that AgRP is a critical regulator of neuronal signaling for zebrafish appetite and energy intake control. Thus, AgRP4.7NTR can be used as a drug-screening platform for therapeutic targets to treat human appetite disorders, including obesity. Furthermore, the unique agrp promoter we identified can be a powerful tool for research on AgRP neurons, especially AgRP neuron-mediated pathways in the hypothalamus, and appetite.

Are gastrointestinal signals the principal guides to human appetite and energy balance?

In view of the exponential rise of global obesity in the past three quarters of the century, it is useful to examine what is driving this change and what approaches can curb it. The chief drivers of weight gain are, on one hand our misunderstanding of the mechanisms controlling energy balance, and, on the other, reliance on current, potentially misleading conflicting scientific opinions and government policies regarding the controls of human appetite. This review outlines the evidence that: (1) there is no direct bioenergetic feedback from energy metabolism or energy stores to the brain mechanisms guiding feeding and energy expenditure, (2) human appetite is controlled by signals originating from an empty or full stomach, food palatability and opportunities to eat as well by the rate of food absorption, that (3) humans bear a genetic burden of having high ability and capacity to store fat and mechanisms that curb body- mass and fat loss, (4) humans are motivated to overconsume while maintaining low energy expenditure, and (5) commercial interests of food businesses marketing highly palatable foods, and wide-spread mechanization of living tasks and urban design reduce the need for physical work and movement. The non-pharmacological and non-surgical solutions to obesity involve an understanding of human genetic impediments and environmental obstacles to maintaining healthy weight, coupled with deliberate corrective or preventive behaviors, such as understanding and using gastrointestinal tract signals that provide sufficient, albeit subtle, cues for sensible food intake, and using daily weight monitoring and activity tracking devices to record and motivate healthy levels of physical activity.

Human loss-of-function variants in the serotonin 2C receptor associated with obesity and maladaptive behavior

Serotonin reuptake inhibitors and receptor agonists are used to treat obesity, anxiety and depression. Here we studied the role of the serotonin 2C receptor (5-HT2CR) in weight regulation and behavior. Using exome sequencing of 2,548 people with severe obesity and 1,117 control individuals without obesity, we identified 13 rare variants in the gene encoding 5-HT2CR (HTR2C) in 19 unrelated people (3 males and 16 females). Eleven variants caused a loss of function in HEK293 cells. All people who carried variants had hyperphagia and some degree of maladaptive behavior. Knock-in male mice harboring a human loss-of-function HTR2C variant developed obesity and reduced social exploratory behavior; female mice heterozygous for the same variant showed similar deficits with reduced severity. Using the 5-HT2CR agonist lorcaserin, we found that depolarization of appetite-suppressing proopiomelanocortin neurons was impaired in knock-in mice. In conclusion, we demonstrate that 5-HT2CR is involved in the regulation of human appetite, weight and behavior. Our findings suggest that melanocortin receptor agonists might be effective in treating severe obesity in individuals carrying HTR2C variants. We suggest that HTR2C should be included in diagnostic gene panels for severe childhood-onset obesity.

CRTC1 deficiency, specifically in melanocortin-4 receptor-expressing cells, induces hyperphagia, obesity, and insulin resistance.

Melanocortin-4 receptor (MC4R) is a critical regulator of appetite and energy expenditure in rodents and humans. MC4R deficiency causes hyperphagia, reduced energy expenditure, and impaired glucose metabolism. Ligand binding to MC4R activates adenylyl cyclase, resulting in increased levels of intracellular cyclic adenosine monophosphate (cAMP), a secondary messenger that regulates several cellular processes. Cyclic adenosine monophosphate responsive element-binding protein-1-regulated transcription coactivator-1 (CRTC1) is a cytoplasmic coactivator that translocates to the nucleus in response to cAMP and is reportedly involved in obesity. However, the precise mechanism through which CRTC1 regulates energy metabolism remains unknown. Additionally, there are no reports linking CRTC1 and MC4R, although both CRTC1 and MC4R are known to be involved in obesity. Here, we demonstrate that mice lacking CRTC1, specifically in MC4R cells, are sensitive to high-fat diet (HFD)-induced obesity and exhibit hyperphagia and increased body weight gain. Moreover, the loss of CRTC1 in MC4R cells impairs glucose metabolism. MC4R-expressing cell-specific CRTC1 knockout mice did not show changes in body weight gain, food intake, or glucose metabolism when fed a normal-chow diet. Thus, CRTC1 expression in MC4R cells is required for metabolic adaptation to HFD with respect to appetite regulation. Our results revealed an important protective role of CRTC1 in MC4R cells against dietary adaptation.

Molecular Mechanisms and Health Benefits of Ghrelin: A Narrative Review.

Ghrelin, an endogenous brain–gut peptide, is secreted in large quantities, mainly from the stomach, in humans and rodents. It can perform the biological function of activating the growth hormone secretagogue receptor (GHSR). Since its discovery in 1999, ample research has focused on promoting its effects on the human appetite and pleasure–reward eating. Extensive, in-depth studies have shown that ghrelin is widely secreted and distributed in tissues. Its role in neurohumoral regulation, such as metabolic homeostasis, inflammation, cardiovascular regulation, anxiety and depression, and advanced cancer cachexia, has attracted increasing attention. However, the effects and regulatory mechanisms of ghrelin on obesity, gastrointestinal (GI) inflammation, cardiovascular disease, stress regulation, cachexia treatment, and the prognosis of advanced cancer have not been fully summarized. This review summarizes ghrelin’s numerous effects in participating in a variety of biochemical pathways and the clinical significance of ghrelin in the regulation of the homeostasis of organisms. In addition, potential mechanisms are also introduced.

The effect of gastrointestinal bitter sensing on appetite regulation and energy intake: A systematic review

Taste receptors are located on the epithelial surface throughout the alimentary canal to identify nutrients and potential toxins. In the oral cavity, the role of taste is to encourage or discourage ingestion, while in the gastrointestinal (GI) tract, the taste receptors help the body prepare for an appropriate response to the ingested foods. The GI sensing of bitter compounds may alter the secretion of appetite-related hormones thereby reducing food intake, which may have potential use for managing health outcomes. This systematic literature review investigated the acute effects of administering different bitter tasting compounds on circulating levels of selected GI hormones, subjective appetite, and energy intake in humans. A literature search was conducted using Medline, CINAHL and Web of Science databases. Of 290 articles identified, 16 met the inclusion criteria. Twelve studies assessed food intake; four of these found bitter administration decreased food intake and eight did not. Fourteen studies assessed subjective appetite; seven found bitter administration affected at least one measure of appetite and seven detected no significant changes. Nine studies included measures of GI hormones; no significant effects were found for changes in GLP-1, CCK or PYY. Four studies measured motilin and ghrelin and found mostly consistent changes in either food intake or subjective appetite. Overall, the data on food intake and subjective appetite were inconsistent, with only motilin and ghrelin responsive to post-oral bitter administration. There is limited consistent conclusive evidence that bitter compounds influence food intake, appetite or hormones with the reasons for this discussed within. Systematic review registrationCRD42021226102.

154-OR: The Site Specific Role of GDF15 in Metformin Action

Metformin lowers glucose levels, appetite and body weight in rodents and humans, but the mechanisms on energy balance regulation have been rarely studied. Metformin increases plasma growth/differentiation factor 15 (GDF15) levels in humans and rodents, while elevating GDF15 via GDF15 infusion in rodents lowers food intake and body weight via its receptor GDNF family receptor α-like (GFRAL) , which is expressed in the hindbrain nucleus area postrema (AP) . However, whether the GDF15-GFRAL axis in the AP mediates metformin effect is unknown. In this study, metformin (200 mg/kg) was infused into the upper small intestine (USI) of rats, while fasting-refeeding study or intravenous glucose tolerance test was performed. USI metformin infusion elevated plasma GDF15 levels (met 138 ± 25 vs. veh 59 ± 7 pg/ml, n = 8, p &amp;lt; 0.01) in parallel to a lowering of food intake (met 30 ± 2 vs. veh 40 ± 2 kcal, n = 16, p &amp;lt; 0.01) and an increase in glucose tolerance (AUC met 5243 ± 75 vs. veh 5674 ± 153, n = 7, p &amp;lt; 0.05) . Further, metformin lowered not only food intake but also body weight gain by 12 h (met 14 ± 1 vs. veh 23 ± 3 g, n = 8, p &amp;lt; 0.01) . Importantly, a knockdown of GFRAL achieved via an injection of lentivirus expressing shRNA GFRAL vs. mismatch into the AP by ∼40% (p &amp;lt; 0.05) negated the ability of metformin to not only lower food intake and body weight, but also increase glucose tolerance independent of body weight. Finally, acute AP GDF15 infusion (2 pmol) decreased food intake (GDF15-25 ± 2 vs. veh-36 ± 3 kcal, n = 10, p &amp;lt; 0.01) and weight gain (as early at 6 h, GDF15 3.6 ± 1.2 vs. vehicle 8.7 ± 1.6 g, n = 10, p &amp;lt; 0.05) , and increased glucose tolerance independently from body weight (AUC, GDF15-5322 ± 94 vs. veh-5722 ± 169, n = 6, p &amp;lt; 0.05) , and these metabolic effects of AP GDF15 infusion were prevented by GFRAL knockdown in the AP. In summary, our findings indicate that the AP GDF15-GFRAL axis is sufficient and necessary for metformin to regulate energy and glucose homeostasis in rodents. Disclosure S.Zhang: None. R.Li: None. Z.Danaei: None. Y.Lim: None. T.K.Lam: None. Funding Canadian Institutes of Health Research (FDN-143204)

The Effects of Vinegar/Acetic Acid Intake on Appetite Measures and Energy Consumption: A Systematic Literature Review

ObjectivesResearch suggests the active ingredient in vinegar, acetic acid, may reduce appetite, thereby reducing energy consumption. This systematic review aimed to assess the effect of vinegar or acetic acid on appetite and subsequent food intake in humans in the published literature. MethodsAll human subject studies, regardless of age or health status. A search using MedLine (Ovid), PubMed, CINAHL Plus, Web of Science, and Cochrane Library between January to April 2021 resulted in 12 papers. One of the publications by Darzi et al. combined the findings of two independent studies and was therefore treated as two separate studies in this review (study 1” and “Darzi study 2). Outcomes included appetite, measured using an appetite rating scale or visual analog scale, satiation, measured as food intake of intervention meal, and satiety, measured as the amount of food intake following vinegar or acetic acid consumption. ResultsSeven short-term studies were crossover randomized controlled trials (RCT) investigating the effect of a single vinegar exposure with satiety or appetite as the primary outcome. Six long-term studies were parallel-group RCTs with repeated vinegar exposure, ranging from 4 to 12 weeks. These studies compared energy intake before and after the vinegar/acetic acid intervention. The short-term interventions indicated that vinegar containing at least 24.6 mmol acetic acid when consumed alongside a meal containing solid foods, acutely suppressed appetite up to 120 minutes postprandially, and ad libitum food intake three- and 24-hours after vinegar consumption. However, results from the long-term studies found no effect on appetite suppression. ConclusionsOverall, four of the six short-term studies reported that vinegar suppressed appetite, while none of the long-term studies were able to reproduce these results. Further research is needed to determine whether oral vinegar consumption may result in long-term appetite reduction, decrease energy intake, and potentially aid in weight loss. Funding SourcesNot applicable.

Abstract No. 316 Percutaneous CT-guided cryovagotomy in patients with class I or class II obesity: a 4-year follow-up

Interruption of vagus nerve signaling has long been associated with loss of appetite in humans, as well as weight loss or attenuation of weight gain in all species studied. In 2017, 20 subjects with Class I or Class II obesity underwent percutaneous CT-guided cryoablation of the posterior vagal trunk to decrease hunger. The purpose of this study was to ascertain and report long-term follow up of these subjects.