Weeks Of Diet Research Articles

Sex differences in the effects of maternal voluntary oral Cannabis consumption on the metabolic outcomes of high-fat diet in adult offspring.

Given the recent rise in Cannabis legalisation, accessibility to Cannabis and consumption have increased during pregnancy. Therefore, there could be unintended developmental consequences. The endocannabinoid system plays a key role in fetal development and later-life energy homeostasis. We explored the long-term effects of maternal voluntary Cannabis consumption on the metabolic outcomes of a high-fat diet (HFD) in adult offspring. Pregnant mice voluntarily consumed Cannabis extract equivalent to 5 mg kg-1day-1 Δ9-tetrahydrocannabinol (THC) from gestational day 1.5 until postnatal day (PD) 10. Pregnancy and pup outcomes and active maternal behaviour were recorded. Male and female offspring (PD49) were placed on a 12-week HFD or control diet; their weight gain, adiposity, glucose tolerance, insulin sensitivity, circulating hormones and pancreatic structure were measured. Perinatal Cannabis exposure (PCE) pup weight was initially reduced but restored by PD16. PCE did not influence weight gain or metabolic characteristics of male mice on a HFD. PCE female but not male offspring on a HFD had reduced accumulation of adipose tissue and lower insulin, leptin and resistin independent of body weight. PCE females on control diet also showed altered basal insulin sensitivity likely because of increased glucagon levels in parallel with reduced islets of Langerhans size and enhanced gene expression of cannabinoid 2 receptors in white adipose tissue. PCE adversely affected glycaemic control in female offspring on control diet while it mitigated HFD-induced metabolic dysfunction. This raises concerns about the long-term effects of PCE on the metabolic health of offspring.

Novel bioactive peptides alleviate Western diet-induced MAFLD in C57BL/6J mice by inhibiting NLRP3 inflammasome activation and pyroptosis via TLR4/NF-κB and Keap1/Nrf2/HO-1 signaling pathways.

Metabolic-associated fatty liver disease (MAFLD) has emerged as a leading chronic liver disease. This condition is characterized by an abnormal accumulation of fat within liver and can progress from simple steatosis to more severe stages involving chronic inflammation and oxidative stress. In this study, we investigated the potential therapeutic effects and underlying mechanism of novel bioactive peptides (EWYF and EWFY) on Western diet-induced MAFLD in C57BL/6J mice. Mice fed a normal chow diet (ND group) and Western diet (WD and treatment groups) for 8weeks. Treatment groups received EWYF and EWFY peptides in low (10mg/kg/day) and high (50mg/kg/day) doses were divided into four groups: EWYF10, EWYF50, EWFY10, and EWFY50. Western diet-induced body weight gain and increased liver weight along with visceral adiposity, which were markedly reversed by bioactive peptides in a dose-dependent manner. Additionally, bioactive peptides significantly reduced hepatic steatosis, liver injury and proinflammatory response. Western diet-induced glucose tolerance and insulin resistance, whereas bioactive peptides significantly improved glucose tolerance and insulin sensitivity. Persistent intake of Western diet triggered chronic inflammation and severe oxidative stress, which were significantly alleviated by bioactive peptides treatment via inhibiting NOD-like receptor protein 3 (NLRP3) inflammasome activation and mitigated pyroptosis by modulating TLR4/NF-κB and Keap1/Nrf2/HO-1 signaling pathways. Furthermore, molecular docking studies suggest that EWYF and EWFY act as fructokinase antagonists and TLR4 inhibitors, which potentially alleviates Western diet-induced MAFLD. Collectively, these findings highlight EWYF and EWFY as promising candidates for MAFLD treatment due to their potent antioxidant and anti-inflammatory properties via specific molecular inhibition.

Perioperative treatment with cilostazol reverses steatosis and improves liver regeneration after major hepatectomy in a steatotic rat model

Cilostazol has previously been shown to reduce liver steatosis and enhance hepatic perfusion. We investigated the effects of cilostazol after major hepatectomy in a steatotic rat model. Six weeks prior to surgery, Sprague–Dawley rats were fed with a high-fructose diet. The treatment group received daily 5 mg/kg cilostazol. Seven days following the cilostazol treatment, all animals underwent 70% liver resection (PHX). Analysis of hepatic blood flow and microcirculation and immunohistochemical examinations were conducted 30 min after PHX (postoperative day [POD] 0) as well as on POD 1, POD 3 and POD 7. The weight of cilostazol-treated animals was significantly reduced compared to untreated controls after completion of the 6-week high-FRC diet. Furthermore, 41% macrovesicular steatosis was found in the control group compared to 8% in the cilostazol group. Hepatic arterial and portal venous perfusion were increased in the cilostazol group on POD 7. Lower liver enzyme release was found postoperatively in cilostazol-treated animals. Moreover, apoptosis and neutrophil infiltration were reduced after cilostazol treatment. Proliferation of hepatocytes and liver regeneration after PHX were significantly increased in the cilostazol group. Consequently, cilostazol should be evaluated as a novel strategy to reduce the rate of liver failure after PHX in steatotic liver.

The impact of ketogenic diet on the frequency of psychogenic non-epileptic seizures (PNES): A feasibility randomized pilot study.

The potential of dietary interventions, particularly the use of the ketogenic diet in patients with Psychogenic Non-Epileptic Seizures (PNES), remains underexplored. This study aimed to assess the feasibility of a 6-week ketogenic diet (Modified Atkins Diet, MAD) intervention in adult patients with PNES and to compare its effects on PNES frequency and other variables against a control healthy diet (CD). A feasibility pilot randomized controlled trial was conducted at a tertiary neurology hospital, enrolling outpatients diagnosed with PNES and assigning them to either MAD or CD. Baseline and follow-up assessments (at 2, 4, and 6 weeks) included evaluation of mental health, PNES frequency, and metabolic measures. Descriptive and inferential methods, including repeated measures ANOVA, were used for statistical analysis. Seventeen patients (mean age 28.23 ± 7.1) were randomly allocated to receive either MAD (n = 12) or CD (n = 5). The entire sample exhibited a significant decrease in monthly PNES frequency (p = 0.01, Hedges ES = 0.618) without differences between groups. The MAD group showed significant improvement in PNES frequency, depression, and anxiety at week six. Results demonstrate that the implementation of MAD is feasible in patients with PNES and suggest that it may reduce seizure frequency and symptoms of depression and anxiety. These findings warrant further investigation in larger, powered studies to demonstrate efficacy. PLAIN LANGUAGE SUMMARY: This study explored the potential benefits of the Modified Atkins Diet (MAD) in reducing the frequency of psychogenic non-epileptic seizures (PNES). The results showed that the diet is safe, well-tolerated, and may decrease the occurrence of PNES, as well as symptoms of depression and anxiety. These findings suggest that dietary modifications could be a helpful complement to PNES treatment, though larger studies are necessary to confirm these outcomes.

DOP097 Emulsifier restriction is an effective therapy for active Crohn’s disease: the ADDapt trial - a multi-centre, randomised, double-blind, placebo-controlled, re-supplementation trial in 154 patients

Abstract Background Food additive emulsifiers result in bacterial dysbiosis, reduced intestinal mucus thickness, microbiota encroachment and increased permeability resulting in intestinal inflammation in murine models. Dietary intervention trials in inflammatory bowel disease are limited by challenges with blinding, high placebo response rates and because changes to one diet component impact on intake of many others (dietary collinearity). The ADDapt trial aimed to investigate the effects of a low emulsifier diet (LED) compared to control diet for 8-weeks on disease activity in patients with mild/moderately active Crohn’s disease (CD). Methods ADDapt (NCT04046913) was an appropriately powered, randomised, double-blind, placebo-controlled, re-supplementation trial (n=154). Patients with a CD activity index (CDAI) of 150-250 plus objective evidence of inflammation (faecal calprotectin (FCP) ≥150 µg/g or endoscopy/radiology) were randomised to either LED (intervention) or LED plus emulsifier re-supplementation (control). Dietary counselling was provided by a dietitian, plus dietary resources and a mobile app to support shopping. To recreate habitual emulsifier intake in controls, both groups received supermarket deliveries for 25% of foods either containing no emulsifiers (intervention) or similar foods containing emulsifiers (control) and were provided three snacks per day that were either emulsifier-free (intervention) or contained carrageenan, carboxymethylcellulose and polysorbate-80 (control). The primary endpoint was the proportion of patients achieving CDAI response (≥70 reduction) at 8-weeks. Secondary endpoints included CDAI remission and FCP. Regression analyses (adjusting for confounders) assessed the difference between trial arms. Results Patients (n=154, ITT population) were recruited from 19 UK centres with 113 (73%) completing the 8-week trial (PP population). Emulsifier intake reduced from median 30.0 (IQR 33.0) to 2.5 (6.0) in the LED group (p<0.001). In the ITT analysis, the primary outcome of CDAI response was achieved in 39 (49.4%) on LED versus 23 (30.7%) in the control group (p=0.019), with an adjusted relative risk (RR) of response of 3.1 (95% CI 1.5, 6.6, p=0.003), a finding that persisted in the PP analysis. In the ITT analysis, compared to control, patients on a LED were more than twice as likely to experience CDAI remission (Adjusted RR 2.1; 95% CI 1.0, 4.4; p=0.042) and >50% reduction in FCP (Adjusted RR 2.9; 95% CI 1.1, 8.0; p=0.039) (Table 1). There were no serious adverse events. Conclusion A LED is an effective treatment in mild/moderately active CD. Ongoing mechanistic analyses will investigate the impact of the LED on gut microbiota and permeability. Funding The Leona M. and Harry B. Helmsley Charitable Trust

Citronellal Alleviates Insulin Resistance in High-Fat Diet/Streptozocin Model: Role of Asprosin/Olfactory Receptor Axis.

Ectopic olfactory receptors are expressed in nonolfactory tissues and perform diverse roles including regulation of glucose homeostasis. We explored the effect of citronellal treatment on olfactory receptor 4M1 subtype (OR4M1) signaling in insulin resistance and Type II diabetes in rats. We aimed to validate the anti-diabetic effect of citronellal through Asprosin/OR4M1 modulation. Exploring new antidiabetics and pharmacological targets is important to improve quality of life and limit complications. The model was established in Sprague-Dawley rats by a high-fat diet for 4weeks followed by a single low-dose streptozotocin (STZ) (35 mg/kg/ip). One week after STZ injection, oral citronellal (100mg/kg) was administered for 4weeks. Citronellal lowered serum glucose and triglycerides and ameliorated OGTT and HOMA-IR results. Docking results revealed that citronellal blocked the Asprosin binding site at OR4M1. The hepatic expression of OR4M1 and Asprosin was reduced. Citronellal lowered cAMP levels causing attenuated levels of protein kinase A and downstream gluconeogenic enzymes: glucose-6-phosphatase and phosphoenolpyruvate carboxykinase. Citronellal also inhibited the expression of hepatic TLR-4 and inhibited JNK phosphorylation. Citronellal attenuated hepatic levels of NF-κB, p-NF-κB, and downstream proteins MCP-1 and TNF-α. These results suggest that citronellal alleviates insulin resistance by mitigating Asprosin/OR4M1 and Asprosin/TLR4/JNK signaling.

Impacts of Copper Deficiency on Oxidative Stress and Immune Function in Mouse Spleen.

Copper is an essential trace element crucial for enzyme synthesis and metabolism. Adequate copper levels are beneficial for maintaining the normal immune function of the spleen. Copper deficiency disrupts the metabolic processes within the spleen and impairs its immune function. This research examines the impact of copper deficiency on the spleen and the potential recovery following copper supplementation. Weaned mice underwent a 4-week copper-deficient diet, succeeded by 1-week of copper repletion via intraperitoneal copper sulfate injection. Histological examination was used to assess pathological changes in the spleen. Biochemical assays were performed to measure oxidative stress levels in the spleen. ELISA, qPCR, and Western blot were employed to examine alterations in inflammatory markers, immune indicators, and oxidative regulatory factors across various levels. Copper deficiency caused histological damage to the spleen, altered the expression of oxidative stress regulatory pathways (Nrf2, Keap1, and HO-1), and affected the expression of key inflammatory enzymes (iNOS, COX2) and transcription factor NF-κB, leading to oxidative damage. This was reflected by decreased levels of SOD, GSH, and T-AOC, along with increased levels of CAT and MDA. The levels of inflammatory cytokines IL-1β, TNF-α, IL-6, and IL-8 were notably increased. Copper supplementation significantly improved these changes. Copper deficiency leads to spleen tissue damage in mice, affecting the Nrf2 regulatory pathway and inducing oxidative damage. Subsequent copper supplementation with copper sulfate effectively ameliorates the damage caused by copper deficiency.

Zinc-Biofortified Rice Improves Growth in Zinc-Deficient Rats.

Biofortification of staple food crops with zinc (Zn) is considered a sustainable strategy to prevent deficiency, but evidence on their health impact is awaited. The weaning Wistar/Kyoto male rats were fed on a Zn-deficient diet (ZDD, < 0.1ppm) for 4weeks followed by repletion (pair feeding) with control rice diet without (CRD; 5.0 ± 0.23ppm) or with additional Zn (CRD + Zn, 30.3 ± 0.60ppm) or biofortified rice diet (BRD; 8.54 ± 0.51ppm) for 3weeks. Body weights, plasma, liver, pancreatic, fecal Zn levels, and intestinal ZIP4 and ZnT1 mRNA expression were measured at the end of the experiment. The body weight of rats fed on CRD or CRD + Zn or BRD significantly increased (p < 0.01) compared to rats fed on ZDD. The body weight BRD was significantly higher compared to CRD (P < 0.01), both of which remained lower compared to CRD + Zn (p < 0.03). Repletion of Zn through either CRD or BRD significantly increased the plasma Zn concentration (PZC), tissue, and fecal Zn excretion compared to ZDD, without significant between-group differences. However, PZC, tissue, and fecal Zn of CRD + Zn was significantly higher compared to the rest of the groups. The intestinal ZIP4 and ZnT1 mRNA expressions are consistent with Zn status and/or dietary Zn exposure. A similar PZC, tissue, and fecal Zn in CRD compared to BRD, despite higher Zn intakes in the latter, could be due to preferential shuttling of Zn for growth. Together, these results indicate that Zn from biofortified rice is efficiently utilized for promoting the growth in Zn-deficient rats.

Effects of a 12 Week Ketogenic Diet Intervention on Obese and Overweight Females with Glucose and Lipid Metabolism Disturbance.

We evaluated the effects of a 12-week hypocaloric ketogenic diet (KD) on glucose and lipid metabolism, as well as body mass, in overweight, obese, and healthy-weight females. One hundred adult females completed the study, including 64 obese (97.99 ± 11.48 kg), 23 overweight (75.50 ± 5.12 kg), and 11 with normal body mass (65.93 ± 3.40 kg). All participants followed a KD consisting of less than 30 g of carbohydrates, approximately 60 g of protein, and 140 g of fat per day (80% unsaturated and 20% saturated fat). Glucose (Gl), insulin (I), glycated haemoglobin (HBA1c), HOMA-IR, triglycerides (TG), and high-density lipoprotein cholesterol (HDL-C) were measured before and after the intervention. Additionally, body mass (BM), BMI (Body Mass Index), waist circumference (WC), hip circumference (HC), and thigh circumference (TC) were recorded. After 12 weeks of the KD, significant improvements were observed in GL, I, TG, HDL-C, HOMA-IR across all groups. Also BM, BMI, TC, WC, and HC were significantly reduced in all participants. Notably, obese participants showed greater reductions in all variables compared to overweight and healthy-weight females. A 12-week KD led to more pronounced improvements in biochemical markers and body mass in obese females compared to other groups. A KD may be particularly beneficial for obese females with hyperglycaemia, hyperinsulinemia, and lipid profile disturbances.

6-Gingerol, a Bioactive Compound of Zingiber officinale, Ameliorates High-Fat High-Fructose Diet-Induced Non-Alcoholic Related Fatty Liver Disease in Rats.

Endoplasmic reticulum (ER) stress has a prominent role in the pathogenesis of high-fat diet-induced non-alcohol related fatty liver disease (NAFLD). The aim of this study is to investigate the effects of 6-G on the reduction of ER stress-induced NAFLD in metabolic syndrome (MetS) rats. Twenty-five male Sprague-Dawley rats were fed with a high-fat high-fructose (HFHF) diet for 16weeks. The rats were treated orally with 6-G (50,100, and 200 mg/kgBW) once daily for eight weeks. At Week 16, all animals were sacrificed, and serum and liver tissue were harvested for biochemical and structural analysis. NAFLD liver rats were shown to have elevated protein expression of GRP78, and ER-associated apoptotic protein, such as IRE1, TRAF2, p-JNK, and p-NF-κB, which were considerably reduced by the 6-G at three doses treatment. Furthermore, a significant increase in liver apoptosis and non-alcoholic steatohepatitis (NAS) score were observed in the NAFLD rat liver and which were also attenuated by the 6-G treatment at three doses. 6-G treatment also reduced ALT, AST, and ALP serum levels. Considering all the findings, it is suggested that the 6-G treatment could be a potential candidate therapy in treating ER stress-induced NAFLD in rats.

Semaglutide alleviates the pancreatic β cell function via the METTL14 signaling and modulating gut microbiota in type 2 diabetes mellitus mice.

Semaglutide, a novel long-acting GLP-1RA, stimulates insulin and suppresses islet-secreted glucagon to reduce glucose levels. It has been unveiled that m6A mRNA modification plays a pivotal role in regulating β cell function. However, it remains unclear whether semaglutide can elicit protective effects through manipulating m6A modification and the underlying mechanism. We aimed to elucidate the role played by semaglutide in m6A modification, and to explore its specific regulatory targets. Furthermore, we also delve into its effects on gut microbiota. Five-week-old male C57BL/6 mice were assigned to two dietary groups and fed a control or high-fat diet for 4weeks. Then T2DM was induced in high-fat diet-fed mice via streptozotocin (STZ), the main groups were resampled to include treatment with semaglutide (SEM, 40μg/kg) for another 4weeks, totaling three groups: Control, Model (T2DM), T2DM+SEM. Additionally, we elucidated specific regulatory targets and signaling pathways in palmitic acid (PA)-stimulated beta-TC-6 cells. Immunofluorescence, Western blot, and RT-qPCR were used in the study. Semaglutide mitigated pancreatic damage, enhanced islet cell proliferation, and restored islet size and alpha- and beta-cell masses. It also improved the expression of METTL14, pancreatic duodenal homeobox 1 (PDX-1), and protecting mitochondria, and modulated the PDX1 expression in an m6A-dependent manner. Concurrently, semaglutide significantly decreases the abundance of Firmicutes, Actinobacteriota, and Lactobacillus, while increasing the Bacteroides and norank_f_Muribaculaceae content, and the production of short-chain fatty acids (SCFA). Semaglutide positively influences by regulating m6A modifications to alleviate pancreatic beta cell dysfunction and modulate the gut microbiome.

Lipopolysaccharide in Bile Promotes the Neutrophil Extracellular Traps-Induced Gallstone Formation by Activating the Gallbladder Immune Barrier.

Cholelithiasis areis a common digestive system disorder, with cholesterol gallstones being the most prevalent type. Gallstones lead to many severe complications, posing a significant burden on global healthcare systems. Many studies have shown associations between biliary microbiota, gallbladder immune microenvironment, and gallstone formation. However, the specific immune mechanisms underlying the cholesterol gallstone formation have not been fully elucidated. In this study, gallbladderand bile samples from 8 asymptomatic patients with cholelithiasis undergoing cholecystectomy and 11healthy liver transplant donors were collected for tissue transcriptome sequencing and differential analysis. Male C57BL/6J mice were fed a normal or lithogenic diet for 6weeks. Starting from the third week, lipopolysaccharide (LPS) or specific regulators were injected intraperitoneally once a week for a total of 3 times. Enzyme-linked immunosorbent assay, quantitative polymerase chain reaction, Western blot, immunohistochemistry, and immunofluorescence were employed for quantitative, qualitative or localization analysis of LPS, neutrophil extracellular traps (NETs), inflammatory factors, proteins, and mRNAs using samples collected from mice. In patients with cholelithiasis, the gallbladder mechanical barrier is impaired, resulting in an immune-activated state. LPS induces damage to the gallbladder mucosal mechanical barrier through the Toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD88)/nuclear factor kappa-B (NF-κB) signaling pathway. Furthermore, it stimulates the continuous production of NETs through the TLR4/Phosphoinositide 3-kinase (PI3K)/Protein kinase B (Akt) signaling pathway, aggravating the formation of gallstones. With the biliary dysbiosis, excessive LPS can invade the submucosa of the gallbladder, leading to chronic inflammation that recruits neutrophils to form NETs, which are ultimately expelled into bile, thereby promoting the formation of gallstones.

Alterations in Glucagon Levels and the Glucagon-to-Insulin Ratio in Response to High Dietary Fat or Protein Intake in Healthy Lean Adult Twins: A Post Hoc Analysis.

Background/Objectives: Emerging data support evidence of the essential role of glucagon for lipid metabolism. However, data on the role of dietary fat intake for glucagon secretion is limited. This analysis investigated whether altering nutritional fat intake affects glucagon levels in healthy subjects. Methods: A total of 92 twins (age: 31 ± 14 years, BMI: 23 ± 3 kg/m2) consumed two 6-week diets: first a low-fat, high-carbohydrate diet (LFD) followed by an isocaloric high-fat, low-carbohydrate diet (HFD). In total, 24 twins (age: 39 ± 15 years, BMI: 24 ± 2 kg/m2) continued with a high-protein diet (HPD). Clinical investigations were performed after 6 weeks of the LFD, after 1 and 6 weeks of the HFD and after 6 weeks of the HPD. Results: The LFD caused a significant decrease in fasting glucagon (-27%, p < 0.001) compared to baseline. After 6 weeks of the HFD, glucagon increased (117%, p < 0.001 vs. LFD), while free fatty acids decreased. Six weeks of the HPD further increased glucagon levels (72%, p = 0.502 vs. HFD), although fasting amino acid levels remained constant. Fasting insulin and HOMA-IR moderately increased after one week of the HFD, while six weeks of the HPD significantly decreased both. The fasting glucagon-to-insulin ratio decreased during the LFD (p < 0.001) but increased after the HFD (p < 0.001) and even further increased after the HPD (p = 0.018). Liver fat, triglycerides and blood glucose did not increase during the HFD. The heritability of glucagon levels was 45% with the LFD. Conclusions: An HFD increases glucagon levels and the glucagon-to-insulin ratio under isocaloric conditions compared to an LFD in healthy lean subjects. This rise in glucagon may represent a metabolic response to prevent hepatic steatosis, as glucagon increases have been previously shown to induce hepatic fat oxidation.

Diet-induced impairment of skeletal muscle and adipose tissue metabolic homeostasis and its prevention by probiotic administration.

Western dietary pattern is one of the main contributors to the increased risk of obesity and chronic diseases, through oxidative stress and inflammation, that are the two key mechanisms targeting metabolic organs, such as skeletal muscle and adipose tissue. The chronic exposure to high levels of dietary fatty acids can increase the amount of intramyocellular lipids in skeletal muscle, altering glucose homeostasis and contributing to a reduction in mitochondrial oxidative capacity. Probiotic administration is a promising approach as preventive strategy to attenuate metabolic damage induced by Western diet. Here, we investigated the beneficial effect of Limosillactobacillus reuteri DSM 17938 on the inflammatory state and oxidative balance in the skeletal muscle and adipose tissue of adult rats fed a western diet for 8weeks, focusing on the role of skeletal muscle mitochondria. Limosillactobacillus reuteri DSM 17938 administration protected the skeletal muscle from mitochondrial dysfunction and oxidative stress, preventing the establishment of inflammation and insulin resistance. Interestingly, a further beneficial effect of the probiotic was exerted on body composition, favoring the deposition of protein mass and preventing adipose tissue hypertrophy and inflammation. These results open the possibility for the use of this probiotic in therapeutic approaches for nutrition-related diseases.

Safety and Effectiveness of a 4-Week Diet on Low-Carb Ready-to-Eat Ketogenic Products as Preoperative Care Treatment in Patients Scheduled for Metabolic and Bariatric Surgery.

Before metabolic and bariatric surgery (MBS), moderate weight loss and liver left lateral section (LLLS) volume reduction are desirable. Low-carb ketogenic diet-induced weight loss before MBS has been shown to have beneficial effects on the reduction in body weight (BW) and LLLS. However, the nutritional protocol of low-carb ketogenic diet may be hard to keep for prolonged periods due to the lack of sweet taste. Furthermore, transitioning to a low-carb ketogenic diet can cause people to crave foods that are restricted in the ketogenic diet, such as cookies, bread, pasta, and bagels. Therefore, many ready-to-eat low-carb ketogenic products (RLCKP) that mimic carbohydrate-rich foods despite a low-carb composition have been provided to make it easier for the patients to adopt a low-carb lifestyle. To date, there are no studies describing the dietary protocol for efficient and safe use of pre-operative RLCKP in terms of weight and LLLS volume reduction in patients with obesity scheduled for MBS. Therefore, the aim of this study was to assess the safety and effectiveness of a 4-week diet using RLCKP in reducing BW and LLLS volume in patients with obesity scheduled for MBS. Patients with obesity (n = 42) with a mean body mass index (BMI) of 42.4 ± 9.2 kg/m2 scheduled for MBS underwent a 4-week preoperative RLCKP diet intervention. Their weight, LLLS volume, and biochemical and metabolic parameters were measured before and after the diet. Patient compliance was assessed by the presence of ketonuria and weight loss. Qualitative methods (5-point Likert questionnaire) were used to measure diet acceptability and side effects. All patients completed the study. We observed highly significant decreases in BW (-6.5%, p < 0.001), and LLLS volume (-22.3%, p < 0.001) and an amelioration of patient clinical status. All patients showed a high frequency of acceptability and compliance in following the diet. No adverse side effects were reported. Based on our findings, we were able to support the hypothesis that a 4-week preoperative RLCKP diet is safe and effective in reducing BW, and LLLS volume in patients with obesity scheduled for MBS.

Western diet promotes endometriotic lesion growth in mice and induces depletion of Akkermansia muciniphila in intestinal microbiota.

Endometriosis, affecting 10% of women in their reproductive years, remains poorly understood. Both individual and environmental unexplained factors are implicated in this heterogenous condition. This study aims to examine the influence of a Western diet on endometriosis lesion development in mice and to uncover the mechanisms involved. Mice were fed either a control diet or a Western diet (high in fatty acids and low in fiber) for 4weeks. Endometriosis was then surgically induced, and lesion development was monitored by ultrasound. After 7weeks, the mice were sacrificed for analysis of lesion characteristics through RT-qPCR, immunohistochemistry, and flow cytometry. Additionally, the intestinal microbiota was assessed using 16S rRNA gene sequencing. Mice on the Western diet developed lesions that were significantly twice as large compared to those on the control diet. These lesions exhibited greater fibrosis and proliferation, alongside enhanced macrophage activity and leptin pathway expression. Changes in the intestinal microbiota were significantly noted after endometriosis induction, regardless of diet. Notably, mice on the Western diet with the most substantial lesions showed a loss of Akkermansia Muciniphila in their intestinal microbiota. A Western diet significantly exacerbates lesion size in a mouse model of endometriosis, accompanied by metabolic and immune alterations. The onset of endometriosis also leads to substantial shifts in intestinal microbiota, suggesting a potential link between diet, intestinal health, and endometriosis development.

Semaglutide normalizes increased cardiomyocyte calcium transients in a rat model of high fat diet-induced obesity.

Obesity increases the risk of heart failure with preserved (HFpEF), but not reduced ejection fraction (HFrEF). The glucagon-like peptide-1 receptor agonist (GLP-1-RA) semaglutide improves outcome of patients with obesity with or without HFpEF, while GLP-1-RAs were associated with adverse outcome in patients with HFrEF. Here, we investigate the effect of in vivo treatment with semaglutide on excitation-contraction coupling in a rat model of obesity. Rats received high-fat/high-fructose diet for 8weeks and were then randomized to semaglutide (HFD/Sema) or vehicle (HFD/Veh) for another 8weeks, during which they could choose between HFD and a low-fat/high-fructose diet (LFD). Control rats received either standard chow (CON), HFD or LFD only, without treatment. After 16weeks, sarcomere shortening and cytosolic Ca2+ concentrations ([Ca2+]c) were determined in isolated cardiomyocytes. Compared with CON, HFD/Veh increased the amplitude of [Ca2+]c transients and systolic sarcomere shortening in absence or presence of β-adrenergic stimulation, which was reversed by HFD/Sema. Caffeine-induced sarcoplasmic reticulum (SR) Ca2+ release and L-type Ca2+ channel (LTCC) currents were reduced by HFD/Sema versus HFD/Veh, while SR Ca2+ ATPase activity remained unaffected. Compared with HFD, LFD increased [Ca2+]c transients and sarcomere shortening further despite similar effects on body weight. While HFD increased cardiomyocyte [Ca2+]c transients and systolic sarcomere shortening, semaglutide normalized these alterations, mediated by reduced SR Ca2+ load and LTCC currents. Because increased LTCC currents were previously traced to cardiac hypertrophy, these effects may explain why GLP-1-RAs provide benefits for patients with obesity with or without HFpEF, but rather adverse outcome in HFrEF.

Exploring diet-induced ketosis with exogenous ketone supplementation as a potential intervention in post-traumatic stress disorder: a feasibility study.

Post-Traumatic Stress Disorder (PTSD) is a severe and pervasive mental disorder, and patients experience numerous distressing symptoms and impairments that significantly impact their lives. In addition to being a mental disorder, PTSD is strongly associated with a wide range of metabolic abnormalities that affect the entire body. Existing treatment options of psychotherapy and medications are often ineffective. Exploring other potential treatments is necessitated. The ketogenic diet has shown potential as a metabolic therapy in certain neurological and mental disorders and is a promising intervention in the treatment of PTSD. This study aimed to examine if a 4-week ketogenic diet intervention supplemented with exogenous ketones (KD-KS) was feasible in adult patients with PTSD, to what extent it was possible to recruit patients, attain and maintain ketosis (plasma concentration of β-hydroxybutyrate (BHB) ≥ 0.5 mmol/L), the occurrence of serious adverse reactions and adverse reactions to KD-KS, and acceptance of treatment. Our exploratory aims were changes in PTSD symptoms and health-related quality of life (QoL) from baseline to 4 weeks. Patients 18 ≤ 65 years old, diagnosed with PTSD, and receiving outpatient treatment for PTSD at Southern Oslo District Psychiatric Centre (DPC), Oslo University Hospital, Oslo, Norway, were included. The intervention consisted of a ketogenic diet supplemented with β-hydroxybutyrate salt to obtain ketosis. PTSD symptoms were measured with the PTSD Checklist for DSM-5 (PCL-5) and QoL was measured with the RAND 36-Item Health Survey 1.0. During a 21-week inclusion period, three of four eligible patients (75% [95% CI: 30 to 95%]) were included. Two patients (67% [95% CI: 21 to 94%]) completed the 4-week intervention and one patient (33% [95% CI: 6 to 79%]) completed 2 weeks of intervention before discontinuing. Ketosis was achieved on day 1 in one patient, and on day 2 in two patients, and was maintained in 87% of the intervention. There were no serious adverse reactions. Adverse reactions were reported in a total of 70% of intervention days, the most frequent being headache followed by fatigue. The participant-perceived degree of adverse reactions was low to moderate. The treatment was accepted by patients on all intervention days. PCL-5 decreased by 20 points (70 to 50) in patient 1 and by 10 points (50 to 40) in patient 2, from baseline to 4 weeks, which is a reliable and clinically meaningful improvement. QoL improved in six of eight RAND-36 subscales in patient 1 and three of eight in patient 2. Patient 3 did not complete assessments after week 2. To the best of our knowledge, this feasibility study is the first study examining a ketogenic diet intervention in patients with PTSD. Three of four predefined feasibility criteria were achieved. Ketosis was attained fast and maintained, patients were compliant and there were clinically meaningful improvements in PTSD symptoms and QoL. Despite the small sample size, the knowledge obtained in this study is important for the planning of future studies with ketogenic diet interventions in this patient group. It is a first step for potential dietary and metabolic therapies in PTSD. Further feasibility and pilot studies with larger sample sizes are needed to determine feasibility and safety before planning future randomised controlled trials investigating an effect. https://ClinicalTrials.gov, identifier NCT05415982.

Fructose restriction has beneficial effects on adipose tissue distribution but not on serum adipokine levels: Post-hoc analysis of a double-blind randomized controlled trial.

We aimed to examine the effects of isocaloric fructose restriction on adipose tissue distribution and serum adipokines. Individuals with BMI >28 kg/m2 (n = 44) followed a 6-week fructose-restricted diet and were randomly allocated to (double-blind) oral supplementation with fructose (control) or glucose (intervention) powder three times daily. Visceral (VAT) and subcutaneous (SAT) adipose tissue was quantified with MRI. Serum interleukin 6 and 8, tumour necrosis factor alpha and adiponectin levels were measured with sandwich immunoassay. BMI decreased in both groups, but the change did not differ between groups (-0.1 kg/m2, 95%CI: -0.3; 0.5). SAT decreased statistically significantly in the control group (-23.2 cm3, 95%CI: -49.4; -4.1), but not in the intervention group. The change in SAT did not differ between groups (29.6 cm3, 95%CI: -1.2; 61.8). No significant differences in VAT were observed within or between study arms. The VAT/SAT ratio decreased statistically significantly in the intervention group (-0.02, 95%CI: -0.04; -0.003) and the change was significantly different between groups (-0.03, 95%CI: -0.54; -0.003). Serum adipokine levels were not affected by the intervention. This study shows that a fructose-restricted diet resulted in a favourable change in adipose tissue distribution, but did not affect serum adipokines. Further studies are warranted to clarify the underlying mechanisms how fructose affects adipose tissue distribution.

Mediterranean Diet-Based Sustainable Healthy Diet and Multicomponent Training Combined Intervention Effect on Body Composition, Anthropometry, and Physical Fitness in Healthy Aging

Background: Diet and exercise interventions have been associated with improved body composition and physical fitness. However, evidence regarding their combined effects in older adults is scarce. This study aimed to investigate the impact of a combined 12-week Mediterranean diet-based sustainable healthy diet (SHD) and multicomponent training (MT) intervention on body composition, anthropometry, and physical fitness in older adults. Methods: Diet intervention groups received a weekly SHD food supply and four sessions, including a SHD culinary practical workshop. The exercise program included MT 50 min group session, three times a week, on non-consecutive days. Body composition and physical fitness variables were assessed through dual X-ray absorptiometry, anthropometric measurements, and senior fitness tests. Repeated measures ANOVA, with terms for group, time, and interaction, was performed. Results: Our results showed that a combined intervention significantly lowered BMI and total fat. Also, significant differences between assessments in all physical fitness tests, except for aerobic endurance, were observed. Adjusted models show significant differences in BMI (p = 0.049) and WHR (p = 0.037) between groups and in total fat (p = 0.030) for the interaction term. Body strength (p &lt; 0.001), balance tests (p &lt; 0.001), and aerobic endurance (p = 0.005) had significant differences amongst groups. Considering the interaction term, differences were observed for upper body strength (p = 0.046) and flexibility tests (p = 0.004 sit and reach, p = 0.048 back scratch). Conclusions: Our intervention study demonstrates the potential of implementing healthy lifestyle and sustainable models to promote healthy and active aging.