Glycaemic and Appetite Suppression Effect of a Vegetable-Enriched Bread

Bread, a frequently consumed food, is an ideal vehicle for addition of ingredients that increase nutrient density and add health benefits. This experimental cross-over study sought to test the effect of a vegetable-enriched bread (VB) in comparison to commercial white bread (WB) and wheatmeal bread (WMB) on serum glucose, insulin response and subjective appetite suppression. On three separate occasions, 10 participants (23 ± 7 years) visited the laboratory and consumed after an overnight fast, in random order, a 75 g serve of WB, WMB or VB. Venous blood samples drawn twice before (0 min) and at 15, 30, 45, 60, 90 and 120 min after consumption of the bread were analysed for glucose and insulin. Participants rated their subjective feelings of hunger, fullness, satisfaction and desire to eat on a 150 mm Likert scale. The mean glucose iAUC over 120 min was not different among the breads. The mean insulin iAUC for the VB was significantly lower than the WB and WMB; difference VB and WB 12,415 pmol/L*minutes (95% CI 1918, 22,912 pmol/L*minutes, p = 0.025) and difference VB and WMB 13,800 pmol/L*minutes (95% CI 1623, 25,976 pmol/L*minutes p = 0.031). The VB was associated with a higher fullness feeling in the participants over the 120-min period. The consumption of VB was associated with less insulin release and higher satiety over 120 min which may be related to the higher fibre content and texture of VB. The role of vegetable and fruit fibres such as pectin in bread and insulin response should also be further explored.

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.

Appetite Suppression and Interleukin 17 Receptor Signaling Activation of Colonic Mycobiota Dysbiosis Induced by High Temperature and High Humidity Conditions

It is known that the microbiome affects human physiology, emotion, disease, growth, and development. Most humans exhibit reduced appetites under high temperature and high humidity (HTHH) conditions, and HTHH environments favor fungal growth. Therefore, we hypothesized that the colonic mycobiota may affect the host’s appetite under HTHH conditions. Changes in humidity are also associated with autoimmune diseases. In the current study mice were fed in an HTHH environment (32°C ± 2°C, relative humidity 95%) maintained via an artificial climate box for 8 hours per day for 21 days. Food intake, the colonic fungal microbiome, the feces metabolome, and appetite regulators were monitored. Components of the interleukin 17 pathway were also examined. In the experimental groups food intake and body weight were reduced, and the colonic mycobiota and fecal metabolome were substantially altered compared to control groups maintained at 25°C ± 2°C and relative humidity 65%. The appetite-related proteins LEPT and POMC were upregulated in the hypothalamus (p < 0.05), and NYP gene expression was downregulated (p < 0.05). The expression levels of PYY and O-linked β-N-acetylglucosamine were altered in colonic tissues (p < 0.05), and interleukin 17 expression was upregulated in the colon. There was a strong correlation between colonic fungus and sugar metabolism. In fimo some metabolites of cholesterol, tromethamine, and cadaverine were significantly increased. There was significant elevation of the characteristic fungi Solicoccozyma aeria, and associated appetite suppression and interleukin 17 receptor signaling activation in some susceptible hosts, and disturbance of gut bacteria and fungi. The results indicate that the gut mycobiota plays an important role in the hypothalamus endocrine system with respect to appetite regulation via the gut-brain axis, and also plays an indispensable role in the stability of the gut microbiome and immunity. The mechanisms involved in these associations require extensive further studies.

Lipocalin 2 mediates appetite suppression during pancreatic cancer cachexia

Lipocalin 2 (LCN2) was recently identified as an endogenous ligand of the type 4 melanocortin receptor (MC4R), a critical regulator of appetite. However, it remains unknown if this molecule influences appetite during cancer cachexia, a devastating clinical entity characterized by decreased nutrition and progressive wasting. We demonstrate that LCN2 is robustly upregulated in murine models of pancreatic cancer, its expression is associated with reduced food consumption, and Lcn2 deletion is protective from cachexia-anorexia. Consistent with LCN2’s proposed MC4R-dependent role in cancer-induced anorexia, pharmacologic MC4R antagonism mitigates cachexia-anorexia, while restoration of Lcn2 expression in the bone marrow is sufficient in restoring the anorexia feature of cachexia. Finally, we observe that LCN2 levels correlate with fat and lean mass wasting and is associated with increased mortality in patients with pancreatic cancer. Taken together, these findings implicate LCN2 as a pathologic mediator of appetite suppression during pancreatic cancer cachexia.

LEPTIN: FROM APPETITE SUPPRESSION TO AUTOIMMUNITY

The hormone leptin is released by adipocytes accordingly to current energy stores to suppress appetite. Apart from this, leptin acts as a proinflammatory cytokine and strongly stimulates inflammation. Immune-modulating properties are partly achieved by affecting T-cell maturation, polarization, and viability. Leptin rises inflammatory cells count, increases proinflammatory cytokine secretion, and impairs regulatory T-lymphocytes differentiation. Leptin secretion and signalization disturbances have recently started to be observed in the context of autoimmunity. In this review, we discuss signaling pathways affected by the satiety hormone, its effect on T-lymphocyte maturation, differentiation and polarization, and relation to other immune-modulating agents. In the end, we highlight the rising evidence connecting hyperleptinemia state which is almost always related to obesity, with autoimmune disorders and take a brief overview of possible mechanisms behind leptin’s potency to induce self-reactivity.

Effects of energy balance on appetite and physiologic mediators of appetite during strenuous physical activity: secondary analysis of a randomized crossover trial

Energy deficit is common during prolonged periods of strenuous physical activity and limited sleep, but the extent to which appetite suppression contributes is unclear. The aim of this randomized crossover study was to determine the effects of energy balance on appetite and physiologic mediators of appetite during a 72-hr period of high physical activity energy expenditure (PAEE, ˜2300kcal/d) and limited sleep designed to simulate military operations (SUSOPS). Ten men consumed an energy-balanced diet while sedentary for 1d (REST) followed by energy balanced (BAL) and energy deficient (DEF) controlled diets during SUSOPS. Appetite ratings, gastric emptying time (GET), and appetite-mediating hormone concentrations were measured. Energy balance was positive during BAL (18±20%) and negative during DEF (-43±9%). Relative to REST, hunger, desire to eat and prospective consumption ratings were all higher during DEF (26±40%, 56±71%, 28±34%, respectively), and lower during BAL (-55±25%, -52±27%, -54±21%, respectively; Pcondition<0.05). Fullness ratings did not differ from REST during DEF, but were 65±61% higher during BAL (Pcondition<0.05). Regression analyses predicted hunger and prospective consumption would be reduced and fullness increased if energy balance were maintained during SUSOPS, and energy deficits of ≥25% would be required to elicit increases in appetite. Between-condition differences in GET and appetite-mediating hormones identified slowed gastric emptying, increased anorexigenic hormone concentrations, and decreased fasting acylated ghrelin concentrations as potential mechanisms of appetite suppression. Findings suggest that physiologic responses that suppress appetite may deter energy balance from being achieved during prolonged periods of strenuous activity and limited sleep.

Understanding the Interplay Between Food Structure, Bacterial Fermentation and Appetite Sensing: A Randomized Crossover Human Trial

Objectives Complex food structures can act like barriers towards digestive enzymes and reduce nutrient bioavailability. Nutrients that escape digestion in the upper gut (mainly fibre), becomes available for bacterial fermentation in the distal gut and generates short chain fatty acids (SCFA) which stimulate the release of appetite suppressing hormones Glucagon like peptide 1 (GLP-1) and Peptide YY (PYY). Processing can alter food structures, leading to more digestible products, but reducing nutrients reaching the distal gut, fermentation and appetite suppression. This study aimed to investigate the impact of food structures on the level of carbohydrate reaching the distal ileum and its subsequent effect on SCFA production and appetite hormone release. Methods Healthy volunteers (n = 10, 18–65 years) attended three separate 4-day inpatient visits. A nasoenteric tube was inserted into their distal ileum. During each visit, participants had one of three dietary interventions: Low fibre, processed diet (LF); High fibre, unprocessed diet (HF); same as HF but domestically processed (HFP). On day 4, ileal, blood and breath hydrogen (BH) samples were collected at baseline and hourly following food intake for 8 h. Blood samples were analyzed for appetite hormones and SCFAs using radioimmunoassay and GC-MS. Ileal samples were analyzed for metabolic profiling using 1H-NMR spectroscopy, partial least squares discriminant analysis with Monte-Carlo cross-validation and repeated-measures design. Results HFP but not HF had higher PYY levels than the LF (P = 0.004). BH and serum total SCFAs were higher in HF and HFP than LF indicating a higher bacterial fermentation (P = 0.021, 0.015 and P = 0.000, 0.003). HFP group had higher total SCFA than HF (P = 0.015). Distinct metabolic differences were identified in ileal samples from groups (e.g., time = 2 h, HF vs HFP R2Y: 0.99, Q2Y: 0.65). Ileal samples will be analysed for microbial profile (16 s rRNA, Illumina MiSeq), glucose and starch (spectroscopy) and SCFAs (GC-MS). Conclusions Current data suggests a potential benefit of domestically processed food structures on appetite suppression as measured by postprandial PYY levels. This may be related to the different metabolic profiles generated in the ileum. Better understanding of this link can aid the design of diets that enhance appetite suppression and reduce food intake. Funding Sources BBSRC.