Diet Feeding Research Articles

Hepatic vagal afferents convey clock-dependent signals to regulate circadian food intake

Circadian desynchrony induced by shiftwork or jet lag is detrimental to metabolic health, but how synchronous or desynchronous signals are transmitted among tissues is unknown. We report that liver molecular clock dysfunction is signaled to the brain through the hepatic vagal afferent nerve (HVAN), leading to altered food intake patterns that are corrected by ablation of the HVAN. Hepatic branch vagotomy also prevents food intake disruptions induced by high-fat diet feeding and reduces body weight gain. Our findings reveal a homeostatic feedback signal that relies on communication between the liver and the brain to control circadian food intake patterns. This identifies the hepatic vagus nerve as a potential therapeutic target for obesity in the setting of chronodisruption.

Restricted Feeding Of Weight Control Diets Induces Weight Loss And Affects Body Composition, Voluntary Physical Activity, Blood Metabolites, Hormones, And Oxidative Stress Markers, And Fecal Metabolites And Microbiota Of Obese Cats.

Feline obesity puts many cats at risk for comorbidities such as hepatic lipidosis, diabetes mellitus, urinary tract diseases, and others. Restricted feeding of specially formulated diets may improve feline health and safely support weight loss while maintaining lean mass. The objective of this study was to determine the effects of restricted intake of weight control diets on weight loss, body composition, voluntary physical activity, serum metabolic and inflammatory markers, and fecal metabolites and microbiota of obese cats. Twenty-four obese adult domestic shorthair cats [body weight (BW) = 5.51 ± 0.92kg; body condition score (BCS) = 8.44 ± 0.53] were used. A leading grocery brand diet was fed during a 4-wk baseline to identify intake needed to maintain BW. After baseline (wk 0), cats were allotted to one of two weight control diets (DRY or CAN) and fed to lose 1.5% BW per wk for 18wk. At baseline and 6, 12, 18wk after weight loss, dual-energy x-ray absorptiometry scans were performed, blood and fecal samples were collected, and voluntary physical activity was measured. Change from baseline data were analyzed statistically using the Mixed Models procedure of SAS, with P<0.05 being significant and P<0.10 being trends. BW was reduced by 1.54 ± 0.51% per wk. Restricted feeding of both diets led to BW (P<0.01) and fat mass loss (P<0.01), reduced BCS (P<0.01), reduced leptin (P<0.01) and insulin (P<0.01) concentrations, and increased superoxide dismutase (P<0.01) and active ghrelin (P<0.01) concentrations. Change from baseline fecal scores were reduced (P<0.01) with restricted feeding and weight loss, while total short-chain fatty acid, acetate, and propionate concentration reductions were greater (P<0.05) in cats fed CAN than those fed DRY. Fecal bacterial alpha diversity measures increased (P<0.01) with restricted feeding and weight loss. Fecal bacterial beta diversity was altered by time in all cats, with wk 0 being different (P<0.05) than wk 6, 12, and 18. Change from baseline relative abundances of 3 fecal bacterial phyla and over 30 fecal bacterial genera were impacted (P<0.05) or tended to be impacted (P<0.10) by dietary treatment. Our data demonstrate that restricted feeding of both weight control diets was an effective means for weight loss in obese adult domestic cats. Some changes were also impacted by diet, highlighting the importance of diet formulation and format, and nutrient composition in weight control diets.

Progress in improving low-cost measurement of feeding behaviors and diets

Information on infant and young child feeding practices and on the diets of vulnerable population groups is needed for global and national monitoring and for evaluating the impacts of interventions. Several population-level indicators have been developed to meet this need, but research to support selection of best data collection practices has been lacking. This supplement brings together a set of recent studies that address measurement issues with the objective of advancing knowledge of best practices, with a focus on low-cost measurement methods. Topics include social desirability bias, recall bias, and the cognitive validity of specific approaches and wording for asking questions on diets. The studies in the supplement provide examples of methods and results that can improve measurement, but also identify gaps and areas where additional work is required.

Nutritional composition of black soldier fly (Hermetia ilucens) larvae reared on vegetable wastes: effects on growth of village chickens

Context Black soldier fly larvae are a promising alternative ingredient in poultry feed. They might be able to replace soybean and fishmeal because the have high concentrations of protein and fat, and are also rich in vitamins and minerals, and because partial replacement of soybean and total replacement of fishmeal produce no adverse effect on the growth performance of village chickens. Therefore, they are a suitable replacement for these traditional ingredients in poultry feed. Aims This study determines the nutritive values of black soldier fly larvae and evaluates the effects of feeding diets containing black soldier fly larvae on the growth performance of village chickens. Methods Samples of black soldier fly larvae were subjected to proximate analysis before a total of 280 1-day-old village chicks were randomly divided into four groups. All groups were fed a basal diet with partial replacements of corn and soybean with black soldier fly larvae at 0% (Control), 5% (T1), 10% (T2) and 15% (T3) for 70 days. Each treatment group consisted of seven replicates, with 10 birds per replicate. The bodyweights, bodyweight gains and feed conversion rates were determined. Key results Dry rendered black soldier fly larvae contained 773.0 ± 0.08 g/kg dry matter, 36.1 ± 0.09 g/kg ash, 408.8 ± 0.28 g/kg crude protein, 283.0 ± 0.16 g/kg ether extract and 40.9 ± 0.44 g/kg crude fibre. The larvae also contained 2.041 MJ/kg of metabolisable energy, 20.4 g/kg of calcium and adequate concentrations of vitamins. The feeding trial showed an average bodyweight gain of 1231.45 ± 23.37 g and feed conversion ratio of 2.03 ± 0.15, which were most efficient with Diet T3. Conclusions Inclusion of 15% black soldier fly larvae in diets can enhance the growth performance of village chickens without adverse effects. Implications Partial replacement of soybean and total replacement of fishmeal in the diet of chickens by black soldier fly larvae are not affecting the growth performance of village chickens but might reduce the feed cost.

Apple Polyphenol Extracts Attenuated Depressive-Like Behaviors of High-Sucrose Diet Feeding Mice by Farnesoid X Receptor-Mediated Modulation of Bile Acid Circulation within the Liver-Gut-Brain Axis.

Although the association between high-sugar diets and depression has been verified, few studies have explored the antidepressant mechanisms of apple polyphenol extracts (APE). Therefore, fifty-four C57BL/6 male mice aged 5 weeks were randomly assigned into five groups: the control group with the standard diet (CON), the constant high-sucrose diet group (HSD), the "2 + 5" alternate diet group (A-HSD), and the 500 mg/(kg·bw) APE treatment for the HSD group (APE) and the A-HSD group (A-APE), respectively. The data of hypothalamic-pituitary-adrenal (HPA) axis function and behavioral experiments confirmed the success in the establishment of depression-like mouse models in both HSD and A-HSD groups, which were significantly alleviated after APE treatment. Meanwhile, APE reduced serum levels of corticosterone and adrenocorticotrophic hormone, alleviated histopathological damage of the liver, colon, and brain, respectively, elevated the protein expressions of Occludin, ZO-1, and MUC-2, and decreased Firmicutes/Bacteroidota ratio and Dubosiella abundance with the increased microbiota of Tannerellaceae_unclassified, Muribaculum, and Lachnospiraceae_unclassified. Moreover, APE treatment reduced Farnesoid X receptor (FXR) protein levels along with the increased expressions of CYP7A1 and TGR5, lowered the contents of serum and fecal total bile acids, and modulated fecal BA compositions, particularly glycocholic acid (GCA) and isolithocholic acid (ILCA). Thus, both the constant and alternate high-sucrose diets successfully induced depression-like behaviors in mice, and APE might be a potential nutraceutical to attenuate high-sucrose diet-induced depression by regulating BAs circulation within the liver-gut-brain axis mediated by FXR.

Assessment of the effect of browse plants’ feed formulation on Goat (&lt;i&gt;Capra aegagrus hircus&lt;/i&gt;) rumen microbial activities and &lt;i&gt;in vitro&lt;/i&gt; gas production

This study assessed the effect of browse Plants feed formulation on Goat (Capra aegagrus hircus) rumen microbial activities and in vitro gas production in Red Sokoto goat (Capra aegagrus hircus) over a period of fourteen (14) weeks. Four selected browse plants- Afzelia africana (TAa) Detarium microcarpum (TDm), Daniellia oliveri (TDo) and Khaya senegalensis (TKs) -were used to formulate diets for animal feeding. Three groups of growing Indigenous Red Sokoto goats were assigned to each of the browse plant diets (BPD), while the control group was placed on a basal diet only. Rumen fluids were collected from the goats intermittently for three (3) consecutive periods, and analyzed for pH, methylene blue-reduction time (MBRT), nitrate reduction, cellulose digestion, glucose fermentation and sedimentation activity rate. The results showed that browse plant feed formulation did not have a significant (p &gt; 0.05) effect on the pH value of the rumen contents. Significant (p &lt; 0.05) reductions in MBRT, nitrate reduction, and glucose fermentation were observed in all treatments except the control diets. However, the period for cellulose digestion significantly increased in all the browse plant-supplemented diet treatments. Furthermore, the volume of gas produced was significantly reduced by 64% (TAa), 62% (TDm), 71% (TDo), and 74% (TKs) in goats fed with browse plants as dietary supplements compared to 7% in the control (Tc). Overall, this study demonstrated that browse plant feed has the potential to significantly reduce the volume of methane produced and released by ruminant animals into the environment.

The mitochondrial enzyme pyruvate carboxylase restricts pancreatic β-cell senescence by blocking p53 activation.

Defective glucose-stimulated insulin secretion (GSIS) and β-cell senescence are hallmarks in diabetes. The mitochondrial enzyme pyruvate carboxylase (PC) has been shown to promote GSIS and β-cell proliferation in the clonal β-cell lines, yet its physiological relevance remains unknown. Here, we provide animal and human data showing a role of PC in protecting β-cells against senescence and maintaining GSIS under different physiological and pathological conditions. β-cell-specific deletion of PC impaired GSIS and induced β-cell senescence in the mouse models under either a standard chow diet or prolonged high-fat diet feeding. Transcriptomic analysis indicated that p53-related senescence and cell cycle arrest are activated in PC-deficient islets. Overexpression of PC inhibited hyperglycemia- and aging-induced p53-related senescence in human and mouse islets as well as INS-1E β-cells, whereas knockdown of PC provoked senescence. Mechanistically, PC interacted with MDM2 to prevent its degradation via the MDM2 binding motif, which in turn restricts the p53-dependent senescent program in β-cells. On the contrary, the regulatory effects of PC on GSIS and the tricarboxylic acid (TCA) anaplerotic flux are p53-independent. We illuminate a function of PC in controlling β-cell senescence through the MDM2-p53 axis.

Dietary oyster mushroom fermented Vachellia erioloba pods enhance Boschveld chicken meat healthiness without altering its physicochemical quality, growth performance and physiology

The high content of fibre and antinutritional phytochemicals limit the utilization of Vachellia erioloba tree pods as nutraceutical feed additive for indigenous chicken diets. The pods can however be solid-state fermented using oyster mushrooms to enhance the nutritional utility of their spent substrate for the nutrition of the native birds. Therefore, this study investigated the effects of dietary incorporation of V. erioloba pods oyster mushroom spent substrate (OMSS) on growth performance, carcass traits, visceral organs, haemato-biochemistry, and meat quality including its fatty acid composition in Boschveld chickens. In a completely randomized design, 250 4-week old mixed gender Boschveld chicks were randomly allotted to 25 pens in which they were offered treatment diets (0, 1.25, 2.5, 5 and 10% OMSS) each with 5 replicates of 10 for 12 weeks and then slaughtered. While there were neither linear nor quadratic effects of diet on overall feed intake (FI) (P > 0.05) and body weight gain (BWG) (P > 0.05), dietary incorporation of OMSS decreased overall feed conversion efficiency (FCE) (quadratic: P < 0.05) particularly in weeks 5 (linear: P < 0.05), 6 (quadratic: P < 0.01) and 11 (quadratic: P < 0.05) with no effects in subsequent weeks (P > 0.05). Also, OMSS induced no effects on all carcass characteristics, visceral organs, haemato-biochemistry and meat physico-chemical quality (P > 0.05) except for the increase in serum albumin (quadratic: P < 0.05) and bilirubin (quadratic: P < 0.05) as well as 24 h post-slaughter meat lightness (linear: P < 0.01), redness (quadratic: P < 0.05), yellowness (linear: P < 0.05), hue angle (quadratic: P < 0.05), and drip loss (quadratic: P < 0.05). Further, the spent substrate decreased meat myristic (linear: P < 0.01), palmitic (linear: P < 0.05), palmitoleic (linear: P < 0.01), and oleic (linear: P < 0.01) acids, as well as its total polyunsaturated fatty acids (PUFAs) (linear: P < 0.05), monounsaturated FAs (MUFAs) (quadratic: P < 0.01), and n-6 PUFAs (linear: P < 0.05). Furthermore, it decreased the meat n-6/n-3 PUFA ratio (quadratic: P < 0.01), with meat from birds fed diets incorporated with 2.5% OMSS eliciting the lowest ratio of 3.63. In contrast, dietary OMSS increased meat stearic (linear: P < 0.001), docosahexaenoic (quadratic: P < 0.01), and tricosanoic (linear: P < 0.001) acid concentrations as well as its total saturated FAs (SFAs) (linear: P < 0.01) and n-3 PUFAs (quadratic: P < 0.01). In conclusion, dietary feeding of V. erioloba pods-derived OMSS enhanced meat nutritional healthiness without majorly altering its physico-chemical quality as well as growth performance, carcass traits, and haemato-biochemistry in Boschveld indigenous chickens. It is recommended for inclusion in indigenous chicken diets at 2.5% level.

Chromatin remodeling by the histone methyltransferase SETD2 drives cardiometabolic heart failure with preserved ejection fraction

Abstract Background Cardiometabolic heart failure with preserved ejection fraction (cHFpEF) is highly prevalent and associates with a poor outcome. Pathological gene expression in heart failure is accompanied by changes in active histone marks without major alterations in DNA methylation. Histone 3 trimethylation at lysine 36 (H3k36me3) - a chromatin signature induced by the histone methyltransferase SETD2 – has shown a strong correlation with changes in gene expression in the human failing heart; however its role in cardiac disease is poorly understood. The present study investigates the role of SETD2/ H3k36me3 in cHFpEF. Purpose To investigate the role of chromatin remodelling in obese HFpEF (obHFpEF). Methods Mice with cardiomyocyte-specific deletion of SETD2 (c-SETD2-/-) were generated and subjected to high fat diet feeding and L-NAME treatment for 15 weeks to induce cHFpEF. Cardiac function and exercise tolerance were assessed by echocardiography and Treadmill exhaustion test, respectively. ChIP-Seq datasets were employed to determine the biological pathways regulated by H3k36me3, whereas chromatin immunoprecipitation assays (ChIP) were performed to investigate SETD2/H3k36me3 enrichment on gene promoters. SETD2 gain- and loss-of-function experiments were performed in cultured cardiomyocytes (CMs) exposed to metabolic stress (palmitic acid). SETD2/H3k36me3 axis was also investigated in left ventricular (LV) myocardial specimens from patients with cHFpEF and control donors. Moreover, pharmacological inhibition of SETD2 was performed in skinned CMs from cHFpEF patients. Results Bioinformatic analysis of ChIP-Seq data in mouse CMs showed a strong involvement of SETD2/H3k36me3 in lipid-related pathways. Specifically, SETD2 and H3k36me3 were upregulated in cHFpEF vs. control mouse hearts and were highly enriched on the promoter of sterol regulatory element-binding transcription factor 1 (SREBP1) gene. SETD2 activation in cHFpEF led to SREBP1 upregulation, myocardial triglyceride accumulation and lipotoxic damage. In cHFpEF mice, cardiomyocyte-specific deletion of SETD2 prevented hypertrophic remodeling, diastolic dysfunction and lung congestion while improving exercise tolerance. Mechanistically, SETD2 deletion blunted H3K36me3 enrichment on SREBP1 promoter thus preventing SREBP1-driven lipid accumulation and leading to a significant rewiring of the cardiac lipidome. These findings were associated with restoration of autophagic flux in the cHFpEF myocardium. In CMs exposed to palmitic acid, SETD2 depletion prevented SREBP1 upregulation, whereas SETD2 overexpression recapitulated lipotoxic damage. Finally, SETD2 was upregulated in LV myocardial samples from cHFpEF patients and its pharmacological inhibition attenuated CM stiffness. Conclusions SETD2 is a new molecular target implicated in the pathophysiology of cHFpEF.

Evaluation of the role of hepatic Gstm4 in diet-induced obesity and dyslipidemia

Obesity and its related diseases continue to rise worldwide, necessitating further investigation to develop new therapeutic strategies. The dysregulation of redox homeostasis is tightly associated with metabolic diseases. Glutathione, an antioxidant, acts as a cofactor for antioxidant and detoxification enzymes such as glutathione S-transferases (GSTs)—a superfamily including Gstm4. So far, the physiological role of Gstm4 remains largely unknown. Human genetics is a powerful tool to discover novel therapeutic targets for metabolic diseases. The single nucleotide polymorphism rs650985, located within the sixth intron of the human gene Gstm4, was associated with plasma lipids, indicating that targeting Gstm4 might intervene in the progression of dyslipidemia. Furthermore, we found that Gstm4 is highly expressed in the liver and enriched in hepatocytes—the parenchymal cells of the liver. We established the mouse model with the hepatic deletion of Gstm4 and found that this mouse model did not present altered body weight, serum lipid profile, or liver fat content in the context of chow or high-fat high cholesterol diet feeding, indicating that hepatic Gstm4 is dispensable for diet-induced obesity and dyslipidemia. Further analysis revealed that hepatic deletion of Gstm4 upregulates the level of protein but not mRNA of Npc1l1—a critical protein mediating cholesterol uptake, suggesting that there might be a link between Gstm4 and lipid metabolic diseases in certain contexts.

Single-cell transcriptomic analysis reveals dynamic activation of cellular signaling pathways regulating beige adipogenesis.

PDGFRA+ cells have been identified as adipocyte stem cells (ASCs) that differentiate into beige adipocytes in white adipose tissue (WAT) following thermogenic stimuli. To elucidate the molecular heterogeneity of ASCs, we conducted single-cell transcriptomic profiling of PDGFRA+ cells isolated from the inguinal WAT (iWAT) of mice treated with the beta3 adrenergic receptor agonist CL316243. Single-cell RNA-seq revealed nine major clusters, which were categorized into four groups: resting, proliferating, differentiating, and adipogenic factor-expressing cells (AFECs). Trajectory analysis revealed sequential activation of molecular pathways, including the Hedgehog and Notch signaling pathways, during beige adipogenesis. AFECs expressed Dpp4 and did not differentiate into adipocytes in culture or after transplantation. Furthermore, genetic lineage tracing studies indicated that DPP4+ cells did not differentiate into adipocytes in iWAT during CL316243-induced beige adipogenesis. However, high-fat diet feeding led to the recruitment of adipocytes from DPP4+ cells in iWAT. Overall, this study improved our understanding of the dynamic molecular basis of beige adipogenesis and the potential contribution of DPP4+ adipocyte lineages to the pathological expansion of WAT during diet-induced obesity.

The BET inhibitor Apabetalone protects against heart failure with preserved ejection fraction by suppressing myocardial inflammation

Abstract Background Posttranslational histone modifications, play a major role in cardiac hypertrophy and dysfunction. Apabetalone (APA), a selective inhibitor of bromodomain and extraterminal containing protein family (BET) proteins, prevents bromodomain-containing protein 4 (BRD4) interactions with chromatin thus modulating transcriptional programs in different organs. Purpose We sought to investigate whether APA could be beneficial in cardiometabolic heart failure with preserved ejection fraction (cHFpEF). Methods Mice were subjected to high fat diet feeding and L-NAME treatment for 15 weeks to induce cHFpEF. Histology, mouse echocardiography (Vevo3100) and Treadmill exhaustion test were performed. Unbiased gene expression profiling by PCR array and proteomics analysis (Olink) was employed in left ventricular (LV) myocardial specimens from HFpEF mice and control animals. Cultured cardiomyocytes (CMs) treated with palmitic acid (PA) were used as an in vitro model of metabolic stress. cHFpEF mice were chronically treated with the BET inhibitor APA (150mg/kg/day) or vehicle (DMSO). In order to translate our findings to the human setting, passive stiffness of skinned CMs collected from cHFpEF patients was assessed before and after APA treatment. Results HFpEF mice displayed LV hypertrophy, diastolic dysfunction, myocardial fibrosis, lung congestion and impaired exercise tolerance as compared to controls. Interestingly, diastolic dysfunction - assessed by E/A ratio and isovolumic relaxation time (IVRT) - and lung congestion were significantly reduced in HFpEF mice treated with APA, while exercise tolerance was improved. Transcriptomic analysis in PA-treated CMs and LV mouse specimens from cHFpEF mice showed a profound deregulation of genes controlling inflammation, namely IL-6, TNF-alpha, and IL-1beta. ChIP assays showed BRD4 occupancy on the promoter of several inflammatory genes, including IL6. Treatment with APA suppressed most of inflammatory genes, with a pronounced effect on IL6 expression. Moreover, APA reduced circulating levels of several inflammatory chemokines. The beneficial effects of APA were explained by modulation of IL-6/CaMKII/STAT3 pathway both in cHFpEF hearts and PA-treated CMs. In skinned CMs from cHFpEF patients, both APA and IL6 blockade were able to attenuate passive stiffness. Conclusions Our findings set the stage for preclinical studies and exploratory clinical trials testing APA in patients with cHFpEF.

Early perturbations to fluid homeostasis alter development of hypothalamic feeding circuits with context-specific changes in ingestive behavior.

Drinking and feeding are tightly coordinated homeostatic events and the paraventricular nucleus of the hypothalamus (PVH) represents a possible node of neural integration for signals related to energy and fluid homeostasis. We used TRAP2;Ai14 and Fos labeling to visualize neurons in the PVH and median preoptic nucleus (MEPO) responding to both water deprivation and hunger. Moreover, we determined that structural and functional development of dehydration-sensitive inputs to the PVH from the MEPO precedes those of agouti-related peptide (AgRP) neurons, which convey hunger signals and are known to be developmentally programmed by nutrition. We also determined that osmotic hyperstimulation of neonatal mice led to enhanced AgRP inputs to the PVH in adulthood, as well as disruptions to ingestive behaviors during high-fat diet feeding and dehydration-anorexia. Thus, development of feeding circuits is impacted not only by nutritional signals, but also by early perturbations to fluid homeostasis with context-specific consequences for coordination of ingestive behavior.

Functional study of amine oxidase copper-containing 1 (AOC1) in lipid metabolism

Amine oxidase copper-containing 1 (AOC1) is a key member of copper amine oxidase family, which is responsible for deamination oxidation of histamine and putrescine. In recent years, AOC1 has been reported to be associated with various cancers, with its expression levels significantly elevated in certain cancer cells, suggesting its potential role in cancer progression. However, its function in lipid metabolism still remains unclear. Through genetic analysis, we have discovered a potential relationship between AOC1 and lipid metabolism. To further investigate, we generated Aoc1 -/- mice and characterized their metabolic phenotypes on both chow diet and high-fat diet (HFD) feeding conditions. On HFD feeding conditions, Aoc1 -/- mice exhibited significantly higher fat mass and impaired glucose sensitivity, and lipid accumulation in white adipose tissue and liver was also increased. This study uncovers the potential role of AOC1 in lipid metabolism and its implications in metabolic disorders such as obesity and type 2 diabetes, providing new targets and research directions for treating metabolic diseases.

Evaluation of fenugreek (Trigonella foenum-graecum L.) powder supplementation on metabolic syndrome, oxidative stress and inflammation in high fat diet fed rats

As an anti-diabetic medicinal plant, fenugreek seed (FG) (Trigonella foenum-graecum L.) has long been utilized and has many therapeutic uses. The current investigation sought to ascertain the effects of FG powder supplementation on insulin resistance, dyslipidemia, and oxidative stress in rats given a high-fat (HF) diet. Measurements of biochemical and antioxidant indicators were made in animal blood and tissue samples, including malondialdehyde (MDA), nitric oxide (NO), advanced oxidation protein product (AOPP), reduced glutathione (GSH), superoxide dismutase (SOD), triglycerides (TG), and catalase (CAT). Furthermore, the tissues of the kidney, heart, and liver were stained histologically. HF diet feeding in rats declined in antioxidant enzyme activities, along with a rise in MDA and other indicators of oxidative stress, which were mitigated by the supplementation of FG. Additionally, FG supplementation enhanced the expression of genes corresponding to antioxidants in the liver of rats given HF diet. FG supplements in HF diet-fed rats displayed altered gene expression in the livers that metabolized fat. Histological staining of the liver demonstrated that FG supplementation reduced necrosis and the accumulation of fat droplets in the liver of rats given HF diets. In conclusion, this finding showed that FG supplementation in HF diet fed rats reduced the plasma lipids, decreased oxidative stress and raised antioxidant enzyme activities. FG may therefore aid in reducing the chronic complications linked to the HF diet in experimental rats.

Mechanisms of Action of Exclusive Enteral Nutrition and Other Nutritional Therapies in Crohn’s Disease

Background and Objectives: Crohn’s disease (CD) is an inflammatory bowel disease (IBD) characterized by transmural inflammation and intestinal fibrosis involving mostly the small intestine and colon. The pathogenic mechanisms of CD remain incompletely understood and cures are unavailable. Current medical therapies are aimed at inducing prolonged remission. Most of the medical therapies such as corticosteroids have substantial adverse effects. Consequently, many dietary therapies have been explored for the management of CD. Up to now, exclusive enteral nutrition (EEN) has been considered the only established dietary treatment for IBD, especially CD. In this article, we aim to give a concise review about the current therapeutic options and challenges in the management of CD and aim to compare the efficacy of EEN with other dietary therapies and update on the possible mechanisms of the benefits of EEN and other nutritional therapies. Methods: We searched the literature up to August 2024 through PubMed, Web of Science, and other sources using search terms such as EEN, nutritional therapy, IBD, Crohn’s disease, ulcerative colitis. Clinical studies in patients and preclinical studies in rodent models of IBD were included in the summary of the therapeutic benefits. Results and Conclusions: EEN involves oral or nasogastric tube feeding of a complete liquid diet with exclusion of normal foods for a defined period (usually 6 to 8 weeks). EEN treatment is demonstrated to have anti-inflammatory and healing effects in CD through various potential pathways, including altering gut bacteria and their metabolites, restoring the barrier function, direct anti-inflammatory action, and indirect anti-inflammatory action by eliminating mechanical stress in the bowel. However, efficacy of other nutritional therapies is not well established in CD, and mechanisms of action are largely unknown.

Targeting Unc5b in macrophages drives atherosclerosis regression and pro-resolving immune cell function

Atherosclerosis results from lipid-driven inflammation of the arterial wall that fails to resolve. Imbalances in macrophage accumulation and function, including diminished migratory capacity and defective efferocytosis, fuel maladaptive inflammation and plaque progression. The neuroimmune guidance cue netrin-1 has dichotomous roles in inflammation partly due to its multiple receptors; in atherosclerosis, netrin-1 promotes macrophage survival and retention via its receptor Unc5b. To minimize the pleiotropic effects of targeting netrin-1, we tested the therapeutic potential of deleting Unc5b in mice with advanced atherosclerosis. We generated Unc5bfl/flCx3cr1creERT2/WT mice, which allowed conditional deletion of Un5b (∆Unc5bMØ) in monocytes and macrophages by tamoxifen injection. After inducing advanced atherosclerosis by hepatic PCSK9 overexpression and western diet feeding for 20 wk, Unc5b was deleted and hypercholesterolemia was normalized to simulate clinical lipid management. Deletion of myeloid Unc5b led to a 40% decrease in atherosclerotic plaque burden and reduced plaque complexity compared to Unc5bfl/flCx3cr1WT/WT littermate controls (CtrlMØ). Consistently, plaque macrophage content was reduced by 50% in ∆Unc5bMØ mice due to reduced plaque Ly6Chi monocyte recruitment and macrophage retention. Compared to CtrlMØ mice, plaques in ∆Unc5bMØ mice had reduced necrotic area and fewer apoptotic cells, which correlated with improved efferocytotic capacity by Unc5b-deficient macrophages in vivo and in vitro. Beneficial changes in macrophage dynamics in the plaque upon Unc5b deletion were accompanied by an increase in atheroprotective T cell populations, including T-regulatory and Th2 cells. Our data identify Unc5b in advanced atherosclerosis as a therapeutic target to induce pro-resolving restructuring of the plaque immune cells and to promote atherosclerosis regression.

Renal denervation ameliorates atrial remodeling in type 2 diabetic rats by regulating mitochondrial dynamics.

There is no effective treatment for diabetes-related atrial remodeling currently. This study aimed to investigate the effects of renal denervation (RDN) on diabetes-related atrial remodeling and explore the related mechanisms. A type 2 diabetes mellitus model was established by high-fat diet feeding and low-dose streptozotocin injection in Sprague‒Dawley rats. After successful modeling, the diabetic rats were randomly assigned to two groups according to whether they were subjected to RDN or sham RDN surgery. At the end of the experiment, cardiac function and structure were evaluated by echocardiography and histology, respectively. Mitochondrial morphology, function and mitochondrial dynamics were assessed by multiple methods. Mdivi1 was used to verify the mechanism by which RDN improves atrial remodeling. In the 10th week, diabetic rats exhibited obvious atrial remodeling, including atrial enlargement and diastolic dysfunction. Pathological staining showed that diabetic rats had cardiomyocyte hypertrophy and interstitial fibrosis in atrial tissues. In terms of mitochondrial morphology and function, diabetic rats exhibited fragmented mitochondria, reduced adenosine triphosphate production and decreased mitochondrial membrane potential levels. Abnormal mitochondrial dynamics in diabetic rats were characterized by the inhibition of mitochondrial fusion, excessive mitochondrial fission, and the suppression of mitophagy. However, RDN effectively ameliorated diabetes-induced pathological atrial remodeling. In addition, RDN significantly improved mitochondrial morphological and functional abnormalities and corrected the disorders of mitochondrial dynamics. Furthermore, the protective effects of RDN against atrial remodeling were related to the regulation of mitochondrial dynamics. RDN prevented diabetes-induced atrial remodeling. These protective effects might be related to improvements in mitochondrial dynamics.

Calorie restriction increases insulin sensitivity to promote beta cell homeostasis and longevity in mice

Caloric restriction (CR) can extend the organism life- and health-span by improving glucose homeostasis. How CR affects the structure-function of pancreatic beta cells remains unknown. We used single nucleus transcriptomics to show that CR increases the expression of genes for beta cell identity, protein processing, and organelle homeostasis. Gene regulatory network analysis reveal that CR activates transcription factors important for beta cell identity and homeostasis, while imaging metabolomics demonstrates that beta cells upon CR are more energetically competent. In fact, high-resolution microscopy show that CR reduces beta cell mitophagy to increase mitochondria mass and the potential for ATP generation. However, CR beta cells have impaired adaptive proliferation in response to high fat diet feeding. Finally, we show that long-term CR delays the onset of beta cell aging hallmarks and promotes cell longevity by reducing beta cell turnover. Therefore, CR could be a feasible approach to preserve compromised beta cell structure-function during aging and diabetes.

Developing a More Sustainable Protein and Amino Acid Supply of Laying Hens in a Split Feeding System.

Two model experiments were conducted to investigate the different protein and amino acid supply of laying hens fed split feeding (SF) diets. In Experiment 1, one conventional (C) and one SF dietary treatment were established, and the diets were implemented for 12 weeks. The concentrations of crude protein, SID Lys, Met, Met + Cys Arg, Val, Thr, Leu, Ile, and Trp of the SF morning diet were the same as in the C diet. The crude protein content of the SF afternoon diet was lower (92%), while the SID values of Lys, Met, Met + Cys were identical compared to the C diet (100%). The SF treatment resulted in a reduced protein/N intake, better feed conversion ratio, higher eggshell thickness and apparent ileal digestibility of Asp, Leu, Lys, Gly, and Ser, and lower concentration of N forms (total, fecal, NH4+, uric acid, urinary) in the excreta compared to the C treatment. In Experiment 2, a control and a low protein (-2% crude protein but the same SID values of Lys, Met, Met + Cys, Thr, Val) SF treatment were compared for 6 weeks. The low protein SF treatment led to a decreased protein/N intake, higher laying rate, lower egg weight, higher ileal digestibility of Ala, Asp, Leu, and Ile, and similar N emission compared to the control SF treatment.