Fat Diet Research Articles

The Impact of Nutritional and Dietary Factors on Hashimoto's Thyroiditis: A Comprehensive Review

Introduction. Hashimoto's disease (HD) is the main cause of hypothyroidism in countries where there is no iodine deficiency in the diet. Characteristic antibodies for it are anti-thyroid peroxidase (anti-TPO) and anti-thyroglobulin (anti-Tg) and their level positively correlates with the severity of HD. Whereas its occurrence is related to genetic, environmental and existential factors. Aim of study. The aim of this study was to analyze dietary factors (protein, fat, vitamin D, iodine, selenium, gluten) and intestinal microbiota on the risk of developing Hashimoto's disease and the influence of each of these factors on its course. Materials and methods. More than 90 articles addressing these issues were analyzed. They were found using the PubMed search engine, and the time frame of these publications covered the last 10 years. Results. Excess iodine is the most important environmental factor influencing the development of Hashimoto's disease. Also, selenium deficiency contributes to the development of HD. On the other hand, the concentration of vitamin D is lower in patients with Hashimoto's disease than in the general population. Furthermore, Vitamin D supplementation reduces the concentration of anti-Tg antibodies. In addition, different types of dietary fat affect thyroid hormone levels differently and a deficiency of protein in the diet causes an increase in TSH and a decrease in thyroid hormones. Moreover, changes in the gut microbiome have been observed in people suffering from Hashimoto's disease. Conclusions. The risk of developing Hashimoto's disease can be increased and decreased by diet and diet allows for the modification of hormone levels in the hypothalamus-pituitary-thyroid axis.

The mitochondrial pyruvate carrier regulates adipose glucose partitioning in female mice

ObjectiveThe mitochondrial pyruvate carrier (MPC) occupies a critical node in intermediary metabolism, prompting interest in its utility as a therapeutic target for the treatment of obesity and cardiometabolic disease. Dysregulated nutrient metabolism in adipose tissue is a prominent feature of obesity pathophysiology, yet the functional role of adipose MPC has not been explored. We investigated whether the MPC shapes the adaptation of adipose tissue to dietary stress in female and male mice. MethodsThe impact of pharmacological and genetic disruption of the MPC on mitochondrial pathways of triglyceride assembly (lipogenesis and glyceroneogenesis) was assessed in 3T3L1 adipocytes and murine adipose explants, combined with analyses of adipose MPC expression in metabolically compromised humans. Whole-body and adipose-specific glucose metabolism were subsequently investigated in male and female mice lacking adipocyte MPC1 (Mpc1AD−/−) and fed either standard chow, high-fat western style, or high-sucrose lipid restricted diets for 24 weeks, using a combination of radiolabeled tracers and GC/MS metabolomics. ResultsTreatment with UK5099 or siMPC1 impaired the synthesis of lipids and glycerol-3-phosphate from pyruvate and blunted triglyceride accumulation in 3T3L1 adipocytes, whilst MPC expression in human adipose tissue was negatively correlated with indices of whole-body and adipose tissue metabolic dysfunction. Mature adipose explants from Mpc1AD−/− mice were intrinsically incapable of incorporating pyruvate into triglycerides. In vivo, MPC deletion restricted the incorporation of circulating glucose into adipose triglycerides, but only in female mice fed a zero fat diet, and this associated with sex-specific reductions in tricarboxylic acid cycle pool sizes and compensatory transcriptional changes in lipogenic and glycerol metabolism pathways. However, whole-body adiposity and metabolic health were preserved in Mpc1AD−/− mice regardless of sex, even under conditions of zero dietary fat. ConclusionsThese findings highlight the greater capacity for mitochondrially driven triglyceride assembly in adipose from female versus male mice and expose a reliance upon MPC-gated metabolism for glucose partitioning in female adipose under conditions of dietary lipid restriction.

The beneficial impact of ketogenic diets on chemically-induced colitis in mice depends on the diet's lipid composition

Previously, we showed that restrictive diets, including ketogenic diet (KD), have an anti-inflammatory impact on the healthy gastrointestinal tract of mice. Afterward, we found that energy-restricting diets mitigate inflammation in the dextran sodium sulfate (DSS) colitis mouse model. The current study aimed to verify the impact of KD on DSS colitis and assess if the diet's fat composition influences the outcomes of the intervention.Mice with mild chronic colitis were fed control chow, KD composed of long-chain triglycerides (KD LCT) or a KD containing a mix of LCT and medium-chain triglycerides (KD LCT/MCT).KDs did not reverse DSS-enhanced gut permeability and shortening of the colon. Both KDs had a similar impact on liver, cecum, and spleen weight, villi and colon length, the thickness of muscularis externa, and expression of ZO-1 and occludin. On the contrary, body weight, glutathione (GSH) and taurine-GSH levels, GSH-S transferase (GST), and myeloperoxidase (MPO) activity, as well as an abundance of several fecal bacteria, all were differentially affected by the two types of KDs. When compared to the DSS control diet, reduction in colon mucosa cytokines expression was stronger in KD LCT than in the KD LCT/MCT group.We conclude that the outcomes of the KD interventions in terms of potential therapeutical applications depend on lipid composition. KD LCT showed a strong positive impact on gut inflammation. A potential contribution of GSH to KD outcomes and a correlation between MPO activity and microbiota composition was identified.

Dietary fat content and supplementation with sodium butyrate: effects on growth performance, carcass traits, meat quality, and myopathies in broiler chickens

This study aimed to evaluate the effects of the dietary inclusion of microencapsulated sodium butyrate (Na-butyrate; 0, 150, and 300 mg Na-butyrate/kg diet) and dietary fat reduction (7.7% vs. 6.7% in the grower diet; 8.9% vs. 7.7% in the finisher diet) in 792 (half male and half female) broiler chickens on growth performance, carcass traits, and meat quality and the occurrence of wooden breast (WB), white striping (WS), and spaghetti meat (SM). Dietary supplementation with Na-butyrate did not affect the growth performance, carcass traits, meat quality traits, or myopathy rates. Dietary fat reduction did not influence feed intake (FI) but decreased average daily gain (ADG); increased feed conversion ratio (FCR) (P < 0.001); and decreased the occurrence of WS (-38%; P < 0.01), WB (-48%; P < 0.05), and SM (-90%; P < 0.01). Dietary fat reduction also increased cold carcass weight (P < 0.01), carcass yield (P < 0.05), and pectoralis major yield (P < 0.05), whereas meat quality was not affected. Compared to females, males had high body weight, ADG, and FI and low FCR (P < 0.001) at the end of the trial. Moreover, cold carcass weight and hind leg yield were higher in males than in females (P < 0.001), whereas females had higher carcass, breast, and p. major yields (P < 0.001). Males showed a higher rate of WB (P < 0.001) and a lower rate of SM (P < 0.01) than females, whereas WS occurrence did not differ between sexes. In conclusion, Na-butyrate supplementation did not affect growth performance, carcass traits, or meat quality. Conversely, the reduction in dietary fat greatly decreased myopathy occurrence, whereas moderately impaired growth performance.

Do we neglect nutrition in childhood interstitial lung disease?

Growth failure and inadequate weight gain are common problems in childhood interstitial lung diseases (chILD) and these children usually need high calories. It is important to manage both pulmonary functions and nutrition as part of their overall treatment plan and early interventions will help children to improve their quality of life and slow the progression of chronic lung disease. Nutritional evaluation on routine clinical follow-up is important, although there are not any specific guidelines for chILD. Nutritional education, high balanced energy, protein, and fat diet will assist to improve weight gain and maintenance of adequate nutrition status in children with ILD.

Abstract We075: Stimulator of Interferon Genes (STING) Regulates T Cell Fate in Cardiometabolic Heart Failure with Preserved Ejection Fraction (HFpEF)

Introduction: Combined obesity and hypertension alter the endoplasmic reticulum (ER) stress response by downregulating X-box binding protein 1 ( Xbp1 ) in T cells, which heightens T cell inflammatory potential and persistence in Heart Failure with Preserved Ejection Fraction (HFpEF), a prevalent syndrome with no cure. The ER protein Stimulator of Interferon Genes (STING), in concert with Xbp1 , coordinates T cell inflammation and death in other contexts, yet its role in the T cell inflammatory response in cardiometabolic HFpEF is unknown. Hypothesis: STING activation and dysregulated ER stress responses drive T cell inflammation in HFpEF by balancing T cell activation and persistence in response to combined comorbidities. Methods: C67BL/6J (wild type, WT) mice were fed high-fat diet/L-NAME (H/L) or standard chow (STD) for 5 weeks, and STING activation was measured in splenic CD4 + T cells by Western blotting. Splenic CD4 + T cells from WT or STING-deficient mice (STING -/- ) were activated with αCD3/αCD28 for 3 days in vitro , then treated with complete media (CM) or CM with 0.2 mM palmitate (abundant in dietary fat)/0.2 mM L-NAME (PALNA) for up to 48 hours. T cell gene expression, activation, and death were assessed using qPCR, flow cytometry, Western blotting, and Lionheart live-cell microscopy. Results: Mice fed H/L had significantly increased splenic T cell expression of phospho-STING, alongside decreased T cell Xbp1 expression and increased cardiac inflammation, compared to STD-fed mice. Ex vivo incubation of CD4 + T cells with PALNA significantly decreased Xbp1 gene expression and increased apoptosis, indicated by cleaved caspase-3 and cleaved poly (ADP-ribose) polymerase (PARP) expression, compared to cells in CM. However, the remaining live PALNA-treated cells showed higher expression of the activation protein CD69, and this was sustained over time, compared to cells in CM. Strikingly, live cell imaging revealed that STING -/- T cells had improved survival and decreased CD69 expression in response to PALNA compared to WT PALNA-treated cells. Conclusions: STING contributes to T cell inflammation in experimental cardiometabolic HFpEF by synergizing with dysregulated ER stress responses to promote the emergence of hyperactivated T cells.

Abstract Mo132: Pouring Salt in the Wound: Sex-specific Cardiometabolic Responses to Increased Dietary Fat, Sugar, and Salt.

Introduction: The general population is becoming more obese, and diabetes rates continue to rise, with overnutrition and consumption of processed foods likely contributing factors. Many people consume diets high in fat, sugar, and salt; however, this triad of factors is rarely examined in unison in studies. In addition, studies that examined diets high in fat and sugar in the context of heart failure with preserved ejection fraction and cardiometabolic outcomes have often performed short dietary interventions, with many studies performed in only male mice, and dietary salt content is often not considered or manipulated. Study Goal: This study aimed to assess the long-term impact of high-fat, high-sucrose diets with differing levels of salt (NaCl) on systemic and cardiovascular physiology in male and female mice. Methods and Results: 12-week-old C57BL/6J male and female mice ( n = 4/group) were fed one of the following diets for 25 weeks: normal chow (NC), low-fat diet (LFD; 10 kcal%), high-fat high sucrose (HFHS; 60 kcal%) with 0.33% NaCl, HFHS with 1% NaCl (HFHS1%), and HFHS with 8% NaCl (HFHS8%). Mice were subjected to basal tail blood metabolite assessment and weighed weekly. In week 24, mice were subjected to glucose tolerance testing, dual-energy X-ray absorptiometry followed by postmortem gravimetric, blood metabolite, histological, and biochemical analyses at 25 weeks. We found that irrespective of sex, body weight was significantly greater in mice receiving HFHS ( p &lt;0.001) and HFHS1% ( p &lt;0.001) versus the other diets. By 25 weeks, male mice were significantly larger than female mice with all diets except HFHS1% ( p &lt;0.05), which correlated with increased percent body fat ( p &lt;0.01), impaired glucose tolerance ( p &lt;0.05) and increased ketone levels ( p &lt;0.05) in female mice subjected to HFHS1% versus males on the same diet. There was also increased heart weight and atrial weights in female mice subjected to HFHS and HFHS1% versus the other females, which was not observed in male mice. Conclusions: Although previous short-term dietary studies have shown that males have altered cardiometabolic responses more than females, our findings together show that long-term dietary interventions with HFHS diets with salt may adversely impact female systemic and cardiovascular physiology.

Apolipoprotein A-I: Potential Protection Against Intestinal Injury Induced by Dietary Lipid.

The intestinal barrier system protects the human body from harmful factors, by continuously renewing the intestinal epithelium, tight junctions and enteric microbes. However, dietary fat can harm the intestinal epithelial barrier enhancing gut permeability. In recent years, Apolipoprotein A-I has attracted much attention because of its anti-inflammatory properties. Numerous studies have demonstrated that Apolipoprotein A-I can regulate mucosal immune cells, inhibit the progression of inflammation, promote epithelial proliferation and repair, and maintain physical barrier function; it can also regulate angiogenesis, thereby improving local circulation. This article is intended to elucidate the mechanism by which Apolipoprotein A-I improves intestinal barrier damage caused by dietary fat and to review the role of Apolipoprotein A-I in maintaining intestinal homeostasis.

Unabsorbed Fecal Fat Content Correlates with a Reduction of Immunoglobulin a Coating of Gut Bacteria in High-Lard Diet-Fed Mice.

Immunoglobulin A (IgA) selectively coats gut bacteria and contributes to regulatory functions in gastrointestinal inflammation and glucose metabolism. Excess intake of lard leads to decrease in the IgA coating of gut bacteria, although the underlying mechanisms remain unknown. This study validates how unabsorbed fat derived from a high-lard diet in the gut affects the IgA coating of bacteria, as assessed in mouse models using three types of dietary fat (lard, medium-, and long-chain triglycerides [MLCTs], and medium-chain triglycerides [MCTs]) exhibiting different digestibilities. C57BL/6J mice are maintained on diets containing lard, MLCTs, or MCTs at 7% or 30% w/w for 10 weeks (n = 6 per group). The fecal fatty acid concentration is measured to quantify unabsorbed fat content. The ratio of IgA-coated bacteria to total bacteria (IgA coating ratio) in the feces is measured by flow cytometry. Compared to lard-fed mice, MLCT- and MCT-fed mice exhibit lower fecal concentrations of palmitic acid, stearic acid, and oleic acid and higher IgA coating ratios at both 7% and 30% dietary fat, and these parameters exhibit significant negative correlations. Unabsorbed fat content in the gut may result in attenuated IgA coating of bacteria in high-lard diet-fed mice.

Effects of black soldier fly (Hermetia illucens) larvae meal on production performance, egg quality, and physiological properties in laying hens: A meta-analysis.

The primary components of fat and protein in chicken diets are fishmeal and soybean; however, due to limited supply and high costs, several efforts have been made to utilize alternative feedstuffs. The potential of black soldier fly larvae (BSFL) as a substitute for fat and protein has been extensively studied, but the findings are not consistent. This study used a meta-analysis approach to investigate the integrated efficacy of BSFL supplementation on laying hen production performance, egg quality, and physiological properties. The articles were retrieved from PubMed, Scopus, ScienceDirect, Cochrane Library, and ProQuest. The retrieved references were examined for potential inclusion. The relevant findings of the included studies were then extracted. Fixed-effects, standard mean difference, 95% confidence intervals, and heterogeneity models were analyzed using the Review Manager website version (Cochrane Collaboration, UK). A total of 24 papers from 17 different nations across five continents have been selected for meta-analysis out of the 3621 articles that were reviewed. The current meta-analysis demonstrated that providing BSFL meals significantly favored feed efficiency, haugh units, albumen quality, eggshell quality, serum glucose, and lipid levels. In addition, significant trends in alanine transaminase, alkaline phosphatase, magnesium, phosphorus, chlorine, and iron levels were observed in blood urea nitrogen, uric acid, creatinine, lactate dehydrogenase, creatine kinase, glutathione peroxidase, and malondialdehyde. On the other hand, it was revealed that there was no favorable effect on weight gain, laying, yolk quality, and hematological profile. The meta-analysis confirmed that BSFL meals can be utilized to optimize feed efficiency, haugh units, albumen, eggshell quality, liver, renal, and cellular physiology of laying hens, although they did not significantly increase body weight gain, laying production, and hematological profiles.

Dietary Milk Phospholipids Increase Body Fat and Modulate Gut Permeability, Systemic Inflammation, and Lipid Metabolism in Mice

The study aimed at how dietary milk polar lipids affect gut permeability, systemic inflammation, and lipid metabolism during diet-induced obesity (DIO). C57BL/6J mice (n = 6x3) were fed diets with 34% fat as energy for 15 weeks: (1) modified AIN-93G diet (CO); (2) CO with milk gangliosides (GG); (3) CO with milk phospholipids (MPL). Gut permeability was assessed by FITC-dextran and sugar absorption tests. Intestinal tight junction proteins were evaluated by Western blot. Plasma cytokines were measured by immunoassay. Body composition was assessed by magnetic resonance imaging. Tissue lipid profiles were obtained by thin layer chromatography. Hepatic expression of genes associated with lipid metabolism was assessed by RT-qPCR. MPL increased the efficiency of converting food into body fat and facilitated body fat accumulation compared with CO. MPL and GG did not affect fasting glucose or HOMA-IR during DIO. MPL increased while GG decreased plasma TG compared with CO. MPL decreased phospholipids subclasses in the muscle while increased those in the liver compared with CO. GG and MPL had little effect on hepatic expression of genes associated with lipid metabolism. Compared with CO, MPL decreased polar lipids content in colon mucosa. Small intestinal permeability decreased while colon permeability increased and then recovered during the feeding period. High-fat feeding increased plasma endotoxin after DIO but did not affect plasma cytokines. MPL and GG did not affect plasma endotoxin, adipokines and inflammatory cytokines. After the establishment of obesity, MPL increased gut permeability to large molecules but decreased intestinal absorption of small molecules while GG tended to have the opposite effects. MPL and GG decreased mannitol and sucralose excretions, which peaked at d 45 in the CO group. MPL decreased occludin in jejunum mucosa compared with CO. GG and MPL did not affect zonula occludens-1 in gut mucosa. In conclusion, during DIO, milk GG decreased gut permeability, and had little effect on systemic inflammation and lipid metabolism; MPL facilitated body fat accumulation, decreased gut permeability, did not affect systemic inflammation.

Effect of daily avocado consumption for 6 mo compared with habitual diet on red blood cell fatty acid profiles and association with cardiometabolic risk factors in individuals with abdominal obesity: a randomized trial

BackgroundAvocado intake improves dietary fat quality, but the subsequent impact on red blood cell (RBC) saturated (SFA), monounsaturated (MUFA), polyunsaturated (PUFA), and trans-fatty acid (TFA) composition and association with cardiometabolic health, has not been elucidated. ObjectivesTo compare the effect of consuming 1 avocado/d relative to habitual diet (HAB) on RBC-FA profiles, and their association with visceral adiposity and cardiometabolic risk factors (CMRFs) in individuals with abdominal obesity. MethodsRBC-FA profiling at baseline, 3- and 6 mo was conducted in participants (n = 994) from the Habitual Diet and Avocado Trial (HAT). HAT was a multisite, free-living, parallel-arm intervention study in which participants were randomly assigned to either the avocado-supplemented group (AVO, usual diet with 1 avocado/d) or the HAB group (usual diet with limited avocado intake) for 6 mo. Changes in RBC-FA profiles, a secondary outcome measure, were determined within and between groups using linear regression and mixed effect models, adjusting for age, sex, BMI, clinical site, smoking status, and percentage of energy intake from fat at baseline. The association between changes in RBC-FAs with visceral adiposity measures and CMRFs was assessed after covariate and False Discovery Rate (FDR <0.05) adjustment. ResultsNo major differences in RBC-FA profiles were observed between groups, with the exception of MUFA cis-vaccenic [18:1n−7c], which was significantly higher in AVO (β: 0.11 [0.05, 0.17]) compared with the HAB (β: 0.03 [−0.03, 0.08]) participants. In the HAB but not AVO group, increases in MUFA cis (18:1n−7c, oleic [18;1n−9c], erucic [22:1n−9c]) and MUFA trans (palmitelaidic [16:1n−7t], vaccenic [18:1n−7t], elaidic [18:1n−9t], and petroselaidic [18;1n−10-12t), as well as PUFA γ-linolenic [18:3n−6], dihomo-γ-linolenic [20:3n−6], arachidonic [20:4n−6], and α-linolenic [18:3n−3] were associated with unfavorable changes in visceral adiposity measures, lipid profiles, glucose, insulin and high sensitivity C-reactive protein concentrations. ConclusionsDaily avocado intake over 6-mo modified RBC–MUFA composition, notably 18:1n−7c, and potentially mitigated some of the unfavorable individual RBC-FA–CMRF associations observed over time in the HAB group.This trial was registered at https://clinicaltrials.gov/study as NCT03528031.

Toxicological effect of deltamethrin on enzymatical, apoptosis and immune response, histological morphology in Litopenaeus vannamei

Deltamethrin (DM) use in agricultural production and storage can result in the presence of residues in several feed ingredients, which can then be ingested by aquatic animals, potentially leading to adverse health effects. Although the potential toxicity of the lipophilic deltamethrin has been evaluated in several studies, there is a paucity of comprehensive studies on the negative effects induced by chronic exposure of shrimp to deltamethrin at different dietary lipid levels. A feeding experiment of six weeks was carried out to assess whether alterations in dietary lipid levels have an impact on the toxicity of DM. In a feeding experiment on Litopenaeus vannamei, the effects of dietary fat levels on the toxicity of DM were studied. There were six distinct diets created comprising three levels of DM (0.2 mg⋅kg–1, 1 mg⋅kg–1, 5 mg⋅kg–1), and two lipid levels (6.96 %, 10.88 %). The diets were designated as LF0.2, LF1, LF5, HF0.2, HF1, HF5. The growth performance and whole shrimp body lipid were reduced with the increase of DM addition to the diet, and DM caused abnormal changes in lipoproteins (LDL, HDL, LPS) in shrimp when feeding diets containing high doses of DM. Furthermore, GOT, GPT, AKP, and ACP activities were found to be significantly increased by long-term exposure to DM. Meanwhile, the way that genes linked to the nuclear factor kappa-B immune signaling pathway showed a significant increase in the hepatopancreas (dorsal, imd, pelle, ikkβ), intestine (imd, tube, pelle), and muscle (toll, imd, pelle) of shrimp following exposure to DM. Similarly, cellular autophagy genes in the hepatopancreas (atg9, atg12), muscle (atg3, atg9), and intestine (atg3, atg5, atg9, beclin, atg13) were significantly upregulated in a dose-dependent manner after shrimp chronic exposure to DM. Histopathological damage was also induced in the muscles under DM exposure. In summary, chronic exposure to DM resulted in a slowing of growth performance, disruption of lipoprotein metabolism, impairment of hepatopancreatic, intestinal, and muscle-related immune functions, as well as the promotion of autophagy and damage to shrimp muscle.

Obesity Arrhythmias: Role of IL-6 Trans-Signaling.

Obesity is a chronic disease that is rapidly increasing in prevalence and affects more than 600 million adults worldwide, and this figure is estimated to increase by at least double by 2030. In the United States, more than one-third of the adult population is either overweight or obese. The global obesity epidemic is a major risk factor for the development of life-threatening arrhythmias occurring in patients with long QT, particularly in conditions where multiple heart-rate-corrected QT-interval-prolonging mechanisms are simultaneously present. In obesity, excess dietary fat in adipose tissue stimulates the release of immunomodulatory cytokines such as interleukin (IL)-6, leading to a state of chronic inflammation in patients. Over the last decade, increasing evidence has been found to support IL-6 signaling as a powerful predictor of the severity of heart diseases and increased risk for ventricular arrhythmias. IL-6's pro-inflammatory effects are mediated via trans-signaling and may represent a novel arrhythmogenic risk factor in obese hearts. The first selective inhibitor of IL-6 trans-signaling, olamkicept, has shown encouraging results in phase II clinical studies for inflammatory bowel disease. Nevertheless, the connection between IL-6 trans-signaling and obesity-linked ventricular arrhythmias remains unexplored. Therefore, understanding how IL-6 trans-signaling elicits a cellular pro-arrhythmic phenotype and its use as an anti-arrhythmic target in a model of obesity remain unmet clinical needs.

Unraveling cysteine deficiency-associated rapid weight loss.

Forty percent of the US population and 1 in 6 individuals worldwide are obese, and the incidence of this disease is surging globally1,2. Various dietary interventions, including carbohydrate and fat restriction, and more recently amino acid restriction, have been explored to combat this epidemic3-6. We sought to investigate the impact of removing individual amino acids on the weight profiles of mice. Compared to essential amino acid restriction, induction of conditional cysteine restriction resulted in the most dramatic weight loss, amounting to 20% within 3 days and 30% within one week, which was readily reversed. This weight loss occurred despite the presence of substantial cysteine reserves stored in glutathione (GSH) across various tissues7. Further analysis demonstrated that the weight reduction primarily stemmed from an increase in the utilization of fat mass, while locomotion, circadian rhythm and histological appearance of multiple other tissues remained largely unaffected. Cysteine deficiency activated the integrated stress response (ISR) and NRF2-mediated oxidative stress response (OSR), which amplify each other, leading to the induction of GDF15 and FGF21, hormones associated with increased lipolysis, energy homeostasis and food aversion8-10. We additionally observed rapid tissue coenzyme A (CoA) depletion, resulting in energetically inefficient anaerobic glycolysis and TCA cycle, with sustained urinary excretion of pyruvate, orotate, citrate, α-ketoglutarate, nitrogen rich compounds and amino acids. In summary, our investigation highlights that cysteine restriction, by depleting GSH and CoA, exerts a maximal impact on weight loss, metabolism, and stress signaling compared to other amino acid restrictions. These findings may pave the way for innovative strategies for addressing a range of metabolic diseases and the growing obesity crisis.

Pannexin1 deletion in lymphatic endothelium affects lymphatic function in a sex-dependent manner.

The lymphatic network of capillaries and collecting vessels ensures tissue fluid homeostasis, absorption of dietary fats and trafficking of immune cells. Pannexin1 (Panx1) channels allow for the passage of ions and small metabolites between the cytosol and extracellular environment. Panx1 channels regulate the pathophysiological function of several tissues in a sex-dependent manner. Here, we studied the role of Panx1 in lymphatic function, and potential sex-dependent differences therein, in Prox1-CreERT2Panx1fl/fl and Panx1fl/fl control mice. Panx1 expression was higher in lymphatic endothelial cells (LECs) of male mice. Lymphatic vessel morphology was not affected in Prox1-CreERT2Panx1fl/fl male and female mice. Lymphatic drainage was decreased by 25% in male Prox1-CreERT2Panx1fl/fl mice, but was similar in females of both genotypes. Accordingly, only male Prox1-CreERT2Panx1fl/fl mice exhibited tail swelling, pointing to interstitial fluid accumulation in males upon Panx1 deletion in LECs. Moreover, serum triglyceride and free fatty acid levels raised less in Prox1-CreERT2Panx1fl/fl mice of both sexes in an oral lipid tolerance test. Finally, the percentage of migratory dendritic cells arriving in draining lymph nodes was increased in Prox1-CreERT2Panx1fl/fl female mice, but was comparable between male mice of both genotypes. Our results point to a LEC-specific role for Panx1 in the functions of the lymphatic system.

Effects of dietary fat sources on growth performance, lipid metabolism and intestinal health of weaned piglets

ABSTRACT We investigated the effect of different fat sources on growth performance and intestinal health in weaned piglets. A total of 72 21-day-old weaned piglets were divided into 3 groups the CON group with 2.5% soybean oil, TRE1 with 2.5% emulsified balanced oil powder and TRE2 with 2.5% emulsified coconut oil powder. These two experimental oil powders were emulsified with the emulsifier (lysophospholipid). The average daily feed intake in TRE1 was significantly higher than that in CON (P < 0.05). The apparent total tract digestibility (ATTD) of ash in TRE1 was significantly higher than that in CON (P < 0.05). Compared with CON, TRE1 tended to improve ATTD of dry matter (P = 0.075), serum triglyceride (P = 0.062) and serum-free fatty acids (P = 0.090). The jejunal villus width of piglets in TRE1 and TRE2 was significantly increased (P < 0.05) and the duodenal crypt depth was significantly decreased (P < 0.05). Compared with CON, TRE1 significantly increased the mRNA expression levels of jejunal Occludin, Claudin-1 and ZO-1 (P < 0.05). From the results of the present study, we concluded that dietary supplementation of 2.5% emulsified balanced oil powder has more obvious effects on enhancing the growth performance of weaned piglets by improving lipid metabolism, intestinal tissue development and barrier function.

Gut microbiota metabolite indole-3-acetic acid maintains intestinal epithelial homeostasis through mucin sulfation

ABSTRACT The global incidence and prevalence of inflammatory bowel disease (IBD) are gradually increasing. A high-fat diet (HFD) is known to disrupt intestinal homeostasis and aggravate IBD, yet the underlying mechanisms remain largely undefined. Here, a positive correlation between dietary fat intake and disease severity in both IBD patients and murine colitis models is observed. A HFD induces a significant decrease in indole-3-acetic acid (IAA) and leads to intestinal barrier damage. Furthermore, IAA supplementation enhances intestinal mucin sulfation and effectively alleviates colitis. Mechanistically, IAA upregulates key molecules involved in mucin sulfation, including 3’-phosphoadenosine 5’-phosphosulfate synthase 2 (Papss2) and solute carrier family 35 member B3 (Slc35b3), the synthesis enzyme and the transferase of 3’-phosphoadenosine-5’-phosphosulfate (PAPS), via the aryl hydrocarbon receptor (AHR). More importantly, AHR can directly bind to the transcription start site of Papss2. Oral administration of Lactobacillus reuteri, which can produce IAA, contributes to protecting against colitis and promoting mucin sulfation, while the modified L. reuteri strain lacking the iaaM gene (Lactobacillus ΔiaaM ) and the ability to produce IAA fail to exhibit such effects. Overall, IAA enhances intestinal mucin sulfation through the AHR-Papss2-Slc35b3 pathway, contributing to the protection of intestinal homfeostasis.

Impact of dietary fat types on expression levels of dopamine and serotonin transporters in the ileum of broiler chickens

Various types of dietary fats undergo distinct fermentation processes by gut microbes, potentially leading to the production of neurotransmitters that can influence the gut. Serotonin and dopamine are recognized neurotransmitters with positive effects on gut function. A broiler chicken trial was conducted to evaluate the influence of dietary fat types on protein expression of 2 neurotransmitter transporters, dopamine (DAT) and serotonin (5-HTT). A total of 560 day-old (Ross 708) male broiler chicks were randomly assigned to 7 dietary treatments. The experimental treatments included a basal diet of corn-soybean meal (SBM), supplemented with 3% of various fats: poultry fat (CON), olive oil (OLIV), fish oil (FISH), canola oil (CANO), lard (LARD), coconut oil (COCO), or flaxseed oil (FLAX). Bodyweight (BW) and feed conversion ratio (FCR) were recorded. Ileal tissues were aseptically collected to determine the expression levels of DAT and 5-HTT through western blot analysis. In addition, plasma samples were analyzed for reactive oxygen metabolites (d-ROM) tests on d 55. Results showed that dietary fat type inclusion did not have any detrimental effect on growth performance parameters. The expression levels of DAT were higher (P < 0.05) in FLAX treatments compared to CON treatments on d 20 and d 55, respectively. Similarly, with 5-HTT levels, FLAX, CANO, and LARD treatments were higher (P < 0.05) than CON treatments on d 20 and d 55. However, higher levels of oxidative stress (d-ROM values) were recorded in COCO (32.75 Carr U), CANO (29 Carr U), and CON treatments (25.5 Carr U) compared to FLAX (18.5 Carr U; P < 0.05) treatment. These findings suggest that incorporating dietary flaxseed oil at a 3% level in the diet has significant potential to elevate the expression levels of intestinal DAT and 5-HTT without inducing oxidative stress.

Synthesis and pancreatic lipase inhibition activity evaluation ofaurone derivatives with substituents on benzylidene ring

Pancreatic lipase is an essential enzyme for the digestion and absorption of dietary fat. Inhibiting this enzyme is one of the strategies in tackling obesity. To date, orlistat is the only Food and Drug Administration (FDA)-approved drug for obesity treatment via this mechanism. Therefore, there has been a growing interest in exploring novel compounds with natural structural frameworks that can give similar activity with fewer side effects. In this study, we describe the synthesis and pancreatic lipase inhibitory activity evaluation of 10 aurone derivatives with different substituents on the benzylidene ring. Aurone derivatives were synthesised through aldol condensation of benzofuranone and corresponding benzaldehyde derivatives with medium to good yields (45-73%). Pancreatic lipase inhibitory activities of synthesized compounds were determined by UV-Vis spectroscopy with quercetin and orlistat as references. Three aurones were found to have higher I% than quercetin at the same concentration (50 μg/ml). Compound 5c (2-(5’bromo-2’-hydroxybenzylidene)benzofuran-3(2H)-one) exhibited the greatest activity (I%=60.95%), better than quercetin (I%=27.20%) at the concentration of 50 μg/ml