Improvement In Hepatic Steatosis Research Articles

Lipidome Changes Associated with a Diet-Induced Reduction in Hepatic Fat among Adolescent Boys with Metabolic Dysfunction-Associated Steatotic Liver Disease.

Little is known about lipid changes that occur in the setting of metabolic-dysfunction-associated steatotic liver disease (MASLD) regression. We previously reported improvements in hepatic steatosis, de novo lipogenesis (DNL), and metabolomic profiles associated with oxidative stress, inflammation, and selected lipid metabolism in 40 adolescent boys (11-16 y) with hepatic steatosis ≥5% (98% meeting the definition of MASLD). Participants were randomized to a low-free-sugar diet (LFSD) (n = 20) or usual diet (n = 20) for 8 weeks. Here, we employed untargeted/targeted lipidomics to examine lipid adaptations associated with the LFSD and improvement of hepatic steatosis. Our LC-MS/MS analysis revealed decreased triglycerides (TGs), diacylglycerols (DGs), cholesteryl esters (ChE), lysophosphatidylcholine (LPC), and phosphatidylcholine (PC) species with the diet intervention (p < 0.05). Network analysis demonstrated significantly lower levels of palmitate-enriched TG species post-intervention, mirroring the previously shown reduction in DNL in response to the LFSD. Targeted oxylipins analysis revealed a decrease in the abundance of 8-isoprostane and 14,15-DiHET and an increase in 8,9-DiHET (p < 0.05). Overall, we observed reductions in TGs, DGs, ChE, PC, and LPC species among participants in the LFSD group. These same lipids have been associated with MASLD progression; therefore, our findings may indicate normalization of key biological processes, including lipid metabolism, insulin resistance, and lipotoxicity. Additionally, our targeted oxylipins assay revealed novel changes in eicosanoids, suggesting improvements in oxidative stress. Future studies are needed to elucidate the mechanisms of these findings and prospects of these lipids as biomarkers of MASLD regression.

Resolution of metabolic dysfunction‐associated steatohepatitis with estradiol in a transgender female: A case report

AbstractA 16‐year‐old trans female patient presented to our Gender Health Program for gender‐affirming care. Her intake evaluation revealed signs of hepatocellular injury and fibrosis concerning for metabolic dysfunction‐associated steatohepatitis (MASH) and she was referred to a Pediatric Hepatologist. Subsequent delays in initiating hormone therapy caused a decline in her mental health, and she began experiencing suicidal ideations. Gender‐affirming hormone therapy has been shown to significantly reduce depressive symptoms and suicidal ideations in transgender and gender diverse youth, and studies in animal models suggest improvement in hepatic steatosis in response to estrogen. A multidisciplinary meeting with Gender Health, Psychiatry, and Hepatology appropriately weighed the benefits of life‐saving hormone therapy and the possibility of an improvement in her comorbid liver condition with the risk of further liver damage from estrogen therapy. The teams and the patient agreed to start estradiol with subsequent resolution of laboratory and radiographic evidence of MASH.

3-(4-Hydroxy-3-methoxyphenyl) propionic acid contributes to improved hepatic lipid metabolism via GPR41

3-(4-hydroxy-3-methoxyphenyl) propionic acid (HMPA) is a metabolite produced by the gut microbiota through the conversion of 4-hydroxy-3-methoxycinnamic acid (HMCA), which is a widely distributed hydroxycinnamic acid-derived metabolite found abundantly in plants. Several beneficial effects of HMPA have been suggested, such as antidiabetic properties, anticancer activities, and cognitive function improvement, in animal models and human studies. However, the intricate molecular mechanisms underlying the bioaccessibility and bioavailability profile following HMPA intake and the substantial modulation of metabolic homeostasis by HMPA require further elucidation. In this study, we effectively identified and characterized HMPA-specific GPR41 receptor, with greater affinity than HMCA. The activation of this receptor plays a crucial role in the anti-obesity effects and improvement of hepatic steatosis by stimulating the lipid catabolism pathway. For the improvement of metabolic disorders, our results provide insights into the development of functional foods, including HMPA, and preventive pharmaceuticals targeting GPR41.

FRI063 Effectiveness Of Liraglutide In Treating Obesity And Improving Hepatic Steatosis

Abstract Disclosure: A.A. Alfadda: None. A. Masood: None. B.M. Alsuwayni: None. A.M. Alhossan: None. Background: Obesity is a chronic relapsing disease with a multifactorial pathology. Chronic inflammation is an important underlying cause, that is also a reason for development of obesity associated comorbidities including metabolic associated fatty liver disease. Medical management of obesity using glucagon-like peptide 1 (GLP-1) agonists has been effective in achieving weight loss and improvements in glucose and lipid control but effects on liver steatosis occurring with persistence of treatment need to be further elucidated. Methods: A single center, prospective study was undertaken to evaluate the effectiveness of liraglutide in patients with obesity. Participants received daily subcutaneous liraglutide with dose escalation (initial dose of 0.6 mg to maximum of 3.0 mg) following the prescribed guidelines. Anthropometric and laboratory parameters were measured at baseline and after three months of receiving the full dose. Estimation of liver steatosis was performed by FibroScan, using controlled attenuation parameter (CAP), and the hepatic steatosis index (HSI) at baseline and at three months of therapy. Descriptive statistics were reported as percentage or mean ± standard deviation (SD) and P values below 0.05 were considered statistically significant. A sub-group analysis was carried out between patients classified as responders to treatment if they lost ≥ 5% of their initial weight, and non-responders, if they did not. Results: In total 28 patients, 18 females (64%) and 10 males (46%) with obesity, mean age 36 ± 11.6 years and BMI (42 ± 4.8) kg/m2, were recruited for the study. Six patients dropped out because of side effects. Twenty-two patients 8 (36.4%) males and 14 (63.6%) females comprised the study population followed for three months. Significant and clinically meaningful changes in weight (decreased by 5.03%), BMI (decreased by 4.71%), HbA1c (decreased by 5.44%), and CAP (decreased by 14.69%) (all P values &amp;lt; 0.05) were noted in all the patients after three months treatment. Sub-group analysis in responders, 16 patients (72.7%), and non-responders 6 patients (27.3%) at three months of treatment demonstrated decrease weight (from 119.64 ± 11.9 to 108.46 ± 11.6 kg; P &amp;lt; 0.001), BMI (from 42.08 ± 5.7 to 38.31 ± 5.7 kg/ m2; P &amp;lt; 0.001), HbA1c (from 5.80 ± 0.4 to 5.38 ± 0.3%; P &amp;lt; 0.001), and CAP (from 286.69 ± 68.6 to 260.69 ± 53.6 dB/m; P = 0.067) in the responders group. On the other hand, we noted a significant decrease in CAP in non-responders’ group (from 285.17 ± 29 to 242.33 ± 51.2; P = 0.041) with no significant changes were observed in anthropometric measures and laboratory markers. Conclusions: Treatment with liraglutide for a period of 3 months in patients with obesity produced significant weight loss and improvement in hepatic steatosis in most patients. Even though the non-responders did not show improvements in weight loss, they demonstrated significant improvements in hepatic steatosis. Presentation: Friday, June 16, 2023

Cystic fibrosis liver disease in the post-modulator era.

Highly effective modulators of cystic fibrosis transmembrane conductance regulator (CFTR) function have had dramatic impact on pulmonary and nutritional outcomes in persons with cystic fibrosis (pwCF). The impact on liver disease in pwCF was not the focus of the registration trials. The purpose of this review is to assess the current literature on the impact of HEMT on liver disease, progression, regression, and safety. Short-term studies of HEMT in pwCF have shown that there is no significant impact on the frequency of liver enzyme abnormalities. There is no evidence for significant improvement in liver enzymes over time on HEMT therapy. There is conflicting data on improvement in liver fibrosis determined by fibrosis indices (APRI and GPR) or elastography. One study showed improvement, and another showed worsening in younger (<20 years old) pwCF. There are reports of resolution or improvement in hepatic steatosis. There are rare reports of severe acute hepatitis and one report of hepatic decompensation leading to liver transplantation due to drug-induced liver disease. HEMT have not been shown to have a significant impact on improving liver disease or preventing fibrosis with short-term therapy. Longer studies are needed to assess the impact of HEMT on liver disease in pwCF.

Solanum lycocarpum St. Hill. fibrous fraction intake can contribute to counteract diet-induced obesity co-morbidities

Solanum lycocarpum St. Hill is a Brazilian Cerrado fruit popularly known as wolf-apple, lobeira or fruta-do-lobo. The proximate composition of fruta-do-lobo showed that the flour prepared from the fruit's pulp has 23g/100g of fiber, which is considered rich in fiber. Data from the literature suggest that dietary fiber intake can positively decrease body weight gain and its adverse side effects through physiological effects and metabolism modulation. From this perspective, this study aimed to analyze the nutritional effects of the fibrous fraction (FF) obtained after extraction of resistant starch from fruta-do-lobo flour in mice with diet-induced obesity. Swiss mice (n = 22) were randomized into three different groups according to the diet offered: control (AIN 93-G diet), HF (high-fat diet – 4% vegetable oil; 31% lard), and FF (HF diet + 3% fibrous fraction of fruta-do-lobo). It was observed that consuming a diet containing the fibrous fraction (FF) promoted histological changes compared to the obese control group (HF) since the liver weight was lower and there was an improvement in hepatic steatosis. Even so, some biological results were observed in the FF group with a profile more similar to the lean control group than the HF group, namely epididymal tissue weight, liver weight, and kITT. It is important to point out that many variables, such as the duration of the protocol and the doses of supplemented dietary fiber, may be associated with the results observed in the present study. However, there is some evidence that the fibrous fraction of fruta-do-lobo can be used as an ingredient to supplement dietary fiber intake and contribute to health promotion.

1571-P: Plasma FGF5 Concentration Correlates Better with Hepatic Steatosis, Blood Glucose, and Specific Plasma Free Fatty Acids than with Other Tissue Fat Accumulation

A few studies reported an association between fibroblast growth factor-5 (FGF5) and NAFLD. We aimed to elucidate the physiologic implication of FGF5 in NAFLD and obesity. A total of 180 subjects [(24 healthy controls and 156 patients with biopsy-proven NAFLD and/or hepatic fat content (HFC) 5% or more on MRI-PDFF] were included to assess association between HFC and various metabolic factors including body fat and plasma levels of glucose, insulin, FGF5, FGF21, oxyntomodulin, incretins, and some free fatty acids (FFAs). Additionally, we analysed a subgroup of obese patients who would undergo laparoscopic sleeve gastrectomy (LSG) (n=50) to see correlation between changes in metabolic variables related to body weight (BW) and HFC before and 6 months after surgery. Plasma FGF5 correlated better with blood glucose and HFC than with total body fat, HOMR-IR, and visceral fat. In relation to plasma FFAs, both FGF5 and HFC together showed a positive correlation with plasma FFAs such as palmitic acid, linolenic acid, and arachidonic acid, but had an inverse correlation with nervonic acid, docosanoic acid, tetracosanoic acid, and hexacosanoic acid. FGF5 level showed an independent association with blood glucose and MRI-PDFF after adjusting for multiple factors. After LSG, BW decreased by an average of 24.6%, while HFC decreased from 19.5% ± 9.1% to 5.7 ± 2.9%, p &amp;lt;0.01). Plasma FGF5 also decreased after LSG (1625.0 ± 656.8 pg/ml vs. 966.8 ± 339.9 pg/ml, p &amp;lt;0.01). The amount of plasma FGF5 change showed a significant correlation with changes in HFC and blood glucose. In conclusion, our results showed that plasma FGF5 level correlated well with HFC, blood glucose, and specific plasma FFAs and also decreased with the improvement of hepatic steatosis after bariatric surgery. Further researches on the causal relationship between FGF5, glucose and lipid metabolism, and NAFLD are needed. Disclosure D.Lee: None. I.Park: None. Funding National Research Foundation of Korea (2021R1A5A2030333, 2019R1I1A2A02062305)

Effects of dietary sugar restriction on hepatic fat in youth with obesity.

Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease in children. Like adults, children can develop the progressive form of NAFLD, nonalcoholic steatohepatitis (NASH), which is characterized by hepatic inflammation, often in the presence of fibrosis. Children with NAFLD are at higher risk of liver-related complications, metabolic dysfunction, and cardiovascular disease in adulthood. Many factors contribute to the escalating prevalence of NAFLD in the pediatric population, among which are an array of dietary patterns such as overnutrition, poor diet quality, and heavy consumption of fat and sugar, including fructose. Findings from an increasing number of epidemiological studies support a connection between high habitual sugar consumption and NAFLD, especially within the context of obesity, but these studies are not able to demonstrate whether sugar is a contributing factor or instead an indicator of an overall poor diet (or lifestyle) quality. To date, only four randomized controlled dietary interventions assessing the effects of sucrose/fructose restriction on hepatic fat fraction in youth with obesity have been published. The objectives of this review are to summarize the key findings from these dietary interventions to achieve a better understanding of the strength of the relationship between dietary sugar restriction and liver fat reduction, despite their inherent limitations, and to discuss the potential impact of weight loss and fat mass reduction on improvement in hepatic steatosis.

(397) Long-term Testosterone Therapy in Men with Functional Hypogonadism and Obesity Improves Surrogate Parameters of Liver Function in a Urological Registry Study

Abstract Introduction Hepatic steatosis is highly prevalent in patients with hypogonadism and obesity. Fatty liver is increasingly recognized as cardiovascular risk factor. The gold standard assessment – histological evaluation of liver biopsies – cannot be performed in routine clinical practice. However, the fatty liver index (FLI) can be calculated using the formula by Bedogni: FLI = (e 0.953*loge (triglycerides) + 0.139*BMI + 0.718*loge (ggt) + 0.053*waist circumference - 15.745) / (1 + e 0.953*loge (triglycerides) + 0.139*BMI + 0.718*loge (ggt) + 0.053*waist circumference - 15.745) * 100 (Bedogni G et al. BMC Gastroenterol 2006;6:33). A FLI &amp;lt;30 rules out and a FLI ≥60 rules in fatty liver. Objective to investigate effects of long-term testosterone therapy (TTh) up to 13 years on surrogate parameters of liver function in men with functional hypogonadism and obesity in comparison to an untreated control group. Methods In an ongoing registry study in men with hypogonadism (total testosterone ≤350 ng/mL and at least moderate symptoms on the Aging Males’ Symptoms scale, AMS) in a single urology office, 491 men had functional hypogonadism and obesity (BMI ≥30 kg/m2). 292 men received testosterone undecanoate (TU) injections 1000 mg/12 weeks following an initial 6-week interval (T-group), 199 opted against TTh and served as controls (CTRL). Height was measured at baseline, weight, waist circumference, triglycerides and γ-GT were assessed at each visit and the fatty liver index (FLI) calculated. AST, ALT, and bilirubin were also measured at each visit. Mean absolute measures with standard deviations (SDs) are reported for a duration of 13 years. Results Mean (median) follow-up: T-group 10.1±3.1 (11), CTRL 9.4±3.3 (10) years. Baseline age was 59.5±6.0 (T-group) and 63.0±5.0 years (CTRL) (p&amp;lt;0.0001). Triglycerides decreased from 3.4±0.5 to 2.2±0.1 in the T-group and increased from 3.2±0.5 to 3.9±0.5 in CTRL (p&amp;lt;0.0001 for both). γ-GT (U/L) decreased from 42.9±22.8 to 20.5±6.4 in the T-group and increased from 35.5±11.6 to 61.7±5.9 in CTRL (p&amp;lt;0.0001 for both). AST (U/L) decreased from 38.4±13.3 to 20.8±1.9 in the T-group and increased from 28.6±9.0 to 54.1±11.9 in CTRL (p&amp;lt;0.0001 for both). ALT (U/L) decreased from 41.4±13.7 to 24.7±2.1 in the T-group and increased from 32.7±9.4 to 60.2±13.8 in CTRL (p&amp;lt;0.0001 for both). Bilirubin decreased from 0.53±0.27 to 0.18±0.05 mg/dL in the T-group and increased from 0.44±0.23 to 1.09±0.27 mg/dL in CTRL (p&amp;lt;0.0001 for both). Waist circumference from 115.0±13.2 to 97.5±4.6 cm in the T-group and increased from 118.6±11.4 to 121.2±6.1 cm in CTRL (p&amp;lt;0.0001 for all). BMI decreased from 36.8±3.6 to 28.3±2.1 kg/m2 in the T-group and increased from 33.9±3.3 to 34.9±2.2 kg/m2 in CTRL (p&amp;lt;0.0001 for all). FLI decreased from 95.1±4.6 to 61.3±11.2 in the T-group and increased from 94.1±4.4 to 98.0±1.3 in CTRL (p&amp;lt;0.0001 for both). Conclusions Long-term testosterone therapy in men with functional hypogonadism and obesity improved surrogate parameters of liver function indicating an improvement in hepatic steatosis. All measures deteriorated over time in untreated obese hypogonadal control patients. Disclosure Yes, this is sponsored by industry/sponsor: Bayer AG, Berlin, Germany. Clarification Industry funding only - investigator initiated and executed study. Any of the authors act as a consultant, employee or shareholder of an industry for: Bayer AG.

Sleeve gastrectomy causes weight-loss independent improvements in hepatic steatosis.

Sleeve gastrectomy (VSG) leads to improvement in hepatic steatosis, associated with weight loss. The aims of this study were to investigate whether VSG leads to weight-loss independent improvements in liver steatosis in mice with diet-induced obesity (DIO); and to metabolically and transcriptomically profile hepatic changes in mice undergoing VSG. Mice with DIO were treated with VSG, sham surgery with subsequent food restriction to weight-match to the VSG group (Sham-WM), or sham surgery with return to unrestricted diet (Sham-Ad lib). Hepatic steatosis, glucose tolerance, insulin and glucagon resistance, and hepatic transcriptomics were investigated at the end of the study period and treatment groups were compared with mice undergoing sham surgery only (Sham-Ad lib). VSG led to much greater improvement in liver steatosis than Sham-WM (liver triglyceride mg/mg 2.5 ± 0.1, 2.1 ± 0.2, 1.6 ± 0.1 for Sham-AL, Sham-WM and VSG respectively; p = 0.003). Homeostatic model assessment of insulin resistance was improved following VSG only (51.2 ± 8.8, 36.3 ± 5.3, 22.3 ± 6.1 for Sham-AL, Sham-WM and VSG respectively; p = 0.03). The glucagon-alanine index, a measure of glucagon resistance, fell with VSG but was significantly increased in Sham-WM (9.8 ± 1.7, 25.8 ± 4.6 and 5.2 ± 1.2 in Sham Ad-lib, Sham-WM and VSG respectively; p = 0.0003). Genes downstream of glucagon receptor signalling which govern fatty acid synthesis (Acaca, Acacb, Me1, Acly, Fasn and Elovl6) were downregulated following VSG but upregulated in Sham-WM. Changes in glucagon sensitivity may contribute to weight-loss independent improvements in hepatic steatosis following VSG.

The potential of pomegranate peel (&lt;em&gt;Punica granatum&lt;/em&gt;) in the treatment of obese and glucose-intolerant mice

Obesity is a pandemic condition, absolutely out of control. Food assistance is among the main proposals for the management of the disease. Thus, the aim of this study was to evaluate the potential of aqueous pomegranate extract in a model of obesity, glucose intolerance and hepatic steatosis induced by high-fat diet. The pomegranate extract was obtained from the association of green extraction techniques. Through the crude extract containing punicalagin and ellagic acid (main compounds), extracts with isolated fractions of these compounds were obtained. For the experimental study, Swiss mice were subjected to the obesity induction period for eight weeks. After, were treated for another 30 days with crude extract of 250 mg/kg (group HF+[1]EXT); punicalagin extract isolated 8.35 mg/kg (HF+Punica group); isolated extract of ellagic acid 0.208 mg/kg (group HF+EA), via gavage. Both the crude extract and its subfractions reduced the body weight gain for the HF+Punica group (1.1 g); HF+EA (0.92 g) compared to HF, while the HF+EXT showed significant weight loss (P&lt;0.001). In the glycemic parameters, all extracts were able to reduce blood glucose when compared to the group with HF. Histological data of liver tissue showed improvement in hepatic steatosis, mainly in the crude extract group. Therefore, it was possible to demonstrate that the aqueous extract of the pomegranate peel, obtained by innovative extraction techniques, can be a potential strategy for the treatment and control of obesity.&#x0D;  &#x0D; [1] abbreviations:EXT – extract, EA- acid ellagic, PUNICA – punicalagin.

An updated meta-analysis of effects of curcumin on metabolic dysfunction-associated fatty liver disease based on available evidence from Iran and Thailand

Metabolic dysfunction-associated fatty liver disease (MAFLD) is a common cause of chronic liver disease and can progress to nonalcoholic steatohepatitis and cirrhosis. This study aims to summarize the evidence for the effects of curcumin on MAFLD progression. Studies were identified from Medline and Scopus databases until April 2022. Systematic reviews and meta-analyses (SRMA) and randomized controlled trials (RCT) were selected based on pre-specified criteria. Three reviewers independently extracted data and assessed quality of included studies. Of the 427 identified records, 6 SRMAs and 16 RCTs were included in the analysis. Very high overlap was observed among SRMAs with corrected covered area of 21.9%. From an updated meta-analysis, curcumin demonstrated significant improvement in aspartate and alanine aminotransferase with pooled mean difference [95% confidence interval (CI)] of −3.90 (−5.97, −1.82) and −5.61 (−9.37, −1.85) units/L, respectively. Resolution and improvement of hepatic steatosis was higher in curcumin than control group with pooled relative risk (95% CI) of 3.53 (2.01, 6.22) and 3.41 (1.36, 8.56), respectively. Curcumin supplementation also led to lower fasting blood sugar, body mass index, and total cholesterol. Further trials should be conducted to assess the effect of curcumin on liver histology, especially regarding non-invasive hepatic fibrosis and steatosis.

The potential of pomegranate peel (&lt;em&gt;Punica granatum&lt;/em&gt;) in the treatment of obese and glucose-intolerant mice

Obesity is a pandemic condition, absolutely out of control. Food assistance is among the main proposals for the management of the disease. Thus, the aim of this study was to evaluate the potential of aqueous pomegranate extract in a model of obesity, glucose intolerance and hepatic steatosis induced by high-fat diet. The pomegranate extract was obtained from the association of green extraction techniques. Through the crude extract containing punicalagin and ellagic acid (main compounds), extracts with isolated fractions of these compounds were obtained. For the experimental study, Swiss mice were subjected to the obesity induction period for eight weeks. After, were treated for another 30 days with crude extract of 250 mg/kg (group HF+[1]EXT); punicalagin extract isolated 8.35 mg/kg (HF+Punica group); isolated extract of ellagic acid 0.208 mg/kg (group HF+EA), via gavage. Both the crude extract and its subfractions reduced the body weight gain for the HF+Punica group (1.1 g); HF+EA (0.92 g) compared to HF, while the HF+EXT showed significant weight loss (P&lt;0.001). In the glycemic parameters, all extracts were able to reduce blood glucose when compared to the group with HF. Histological data of liver tissue showed improvement in hepatic steatosis, mainly in the crude extract group. Therefore, it was possible to demonstrate that the aqueous extract of the pomegranate peel, obtained by innovative extraction techniques, can be a potential strategy for the treatment and control of obesity.

The Synergic Effect of a Nutraceutical Supplementation Associated to a Mediterranean Hypocaloric Diet in a Population of Overweight/Obese Adults with NAFLD.

Overweight/obesity is often associated with a non-alcoholic fatty liver disease (NAFLD). The study aim was to investigate the effects of a nutraceutical supplementation associated to a Mediterranean-hypocaloric-diet (MHD) on ultrasound-liver-steatosis (ULS) grade improvement in overweight/obese patients with NAFLD. A total of 68 subjects (BMI ≥ 25 kg/m2) with NAFLD were recruited, randomized into 2 groups and treated for 3 months: the Nutraceutical group was treated with MHD plus nutraceutical supplementation (Vitamin E, L-glutathione, silymarin and hepato-active compounds); the Control-group only with a MHD. Anthropometric measurements, body composition, biochemical parameters and Hepatic steatosis index (HSI) were evaluated at baseline and after 3 months; patients with HSI &gt;36 underwent a liver ultrasound to determine liver steatosis grade (3 severe, 2 moderate, 1 mild). In all patients, a significant improvement in nutritional and biochemical parameters was observed after treatment. After treatment, the nutraceutical group showed a significant improvement in hepatic steatosis, either according to ULS-grade (11.1% and 5.6% of patients with mild and moderate liver steatosis, respectively, showed a complete NAFLD regression; 33.3% and 22.2% of patients with moderate and severe liver steatosis, respectively showed a regression to mild liver steatosis), or according to HSI (49.3 ± 10.1 vs. 43.3 ± 9.0, p = 0.01), suggesting that a healthy diet is still the best choice, although the use of specific supplements can enhance the efficacy of dietary intervention in overweight/obese patients with NAFLD.

Bifidobacterial carbohydrate/nucleoside metabolism enhances oxidative phosphorylation in white adipose tissue to protect against diet-induced obesity

BackgroundComparisons of the gut microbiome of lean and obese humans have revealed that obesity is associated with the gut microbiome plus changes in numerous environmental factors, including high-fat diet (HFD). Here, we report that two species of Bifidobacterium are crucial to controlling metabolic parameters in the Korean population.ResultsBased on gut microbial analysis from 99 Korean individuals, we observed the abundance of Bifidobacterium longum and Bifidobacterium bifidum was markedly reduced in individuals with increased visceral adipose tissue (VAT), body mass index (BMI), blood triglyceride (TG), and fatty liver. Bacterial transcriptomic analysis revealed that carbohydrate/nucleoside metabolic processes of Bifidobacterium longum and Bifidobacterium bifidum were associated with protecting against diet-induced obesity. Oral treatment of specific commercial Bifidobacterium longum and Bifidobacterium bifidum enhanced bile acid signaling contributing to potentiate oxidative phosphorylation (OXPHOS) in adipose tissues, leading to reduction of body weight gain and improvement in hepatic steatosis and glucose homeostasis. Bifidobacterium longum or Bifidobacterium bifidum manipulated intestinal sterol biosynthetic processes to protect against diet-induced obesity in germ-free mice.ConclusionsOur findings support the notion that treatment of carbohydrate/nucleoside metabolic processes-enriched Bifidobacterium longum and Bifidobacterium bifidum would be a novel therapeutic strategy for reprograming the host metabolic homeostasis to protect against metabolic syndromes, including diet-induced obesity.88iFgxnB7AkxSyj5zCNySmVideo

Effect of a Multicomponent Intervention on Hepatic Steatosis Is Partially Mediated by the Reduction of Intermuscular Abdominal Adipose Tissue in Children With Overweight or Obesity: The EFIGRO Project.

In adults, there is evidence that improvement of metabolic-associated fatty liver disease (MAFLD) depends on the reduction of myosteatosis. In children, in whom the prevalence of MAFLD is alarming, this muscle-liver crosstalk has not been tested. Therefore, we aimed to explore whether the effects of a multicomponent intervention on hepatic fat is mediated by changes in intermuscular abdominal adipose tissue (IMAAT) in children with overweight/obesity. A total of 116 children with overweight/obesity were allocated to a 22-week family-based lifestyle and psychoeducational intervention (control group, n = 57) or the same intervention plus supervised exercise (exercise group, n = 59). Hepatic fat percentage and IMAAT were acquired by MRI at baseline and at the end of the intervention. Changes in IMAAT explained 20.7% of the improvements in hepatic steatosis (P < 0.05). Only children who meaningfully reduced their IMAAT (i.e., responders) had improved hepatic steatosis at the end of the intervention (within-group analysis: responders -20% [P = 0.005] vs. nonresponders -1.5% [P = 0.803]). Between-group analysis showed greater reductions in favor of IMAAT responders compared with nonresponders (18.3% vs. 0.6%, P = 0.018), regardless of overall abdominal fat loss. The reduction of IMAAT plays a relevant role in the improvement of hepatic steatosis after a multicomponent intervention in children with overweight/obesity. Indeed, only children who achieved a meaningful reduction in IMAAT at the end of the intervention had a reduced percentage of hepatic fat independent of abdominal fat loss. Our findings suggest that abdominal muscle fat infiltration could be a therapeutic target for the treatment of MAFLD in childhood.

Improvement of hepatic steatosis and fibrosis in diabetes: Which bariatric procedure is more appropriate?

Improvement of hepatic steatosis and fibrosis in diabetes: Which bariatric procedure is more appropriate?

Comparison of delta-tocotrienol and alpha-tocopherol effects on hepatic steatosis and inflammatory biomarkers in patients with non-alcoholic fatty liver disease: A randomized double-blind active-controlled trial

ObjectiveWe aimed to compare the efficacy of δ-tocotrienol with α-tocopherol in the treatment of patients with non-alcoholic fatty liver disease (NAFLD). Design and interventionsThis study was a double-blinded, active-controlled trial. The patients with NAFLD were randomly assigned to receive either δ-tocotrienol 300 mg or α-tocopherol 268 mg twice daily for 48 weeks. EndpointsThe primary endpoints were change from baseline in fatty liver index (FLI), liver-to-spleen attenuation ratio (L/S ratio), and homeostatic model assessment for insulin resistance (HOMA-IR) at 48 weeks. Key secondary endpoints were change in markers of inflammation, oxidative stress, and hepatocyte apoptosis. Clinical assessment, biochemical analysis, and computed tomography scan of the liver were conducted at baseline, 24 and 48 weeks. ResultsA total of 100 patients (δ-tocotrienol = 50, α-tocopherol = 50) were randomized and included in the intention to treat analysis. Compared with baseline, there was a significant improvement (p < .001) in FLI, L/S ratio, HOMA-IR, and serum malondialdehyde in both groups at 48 weeks that was not significant between the two groups. However, there was a significantly greater decrease in body weight, serum interleukin-6, tumor necrosis factor-alpha, leptin, cytokeratin-18, and increase in adiponectin in the δ-tocotrienol group compared to the α-tocopherol group at 48 weeks (p < .05). No adverse events were reported. Conclusionδ-tocotrienol and α-tocopherol exerted equally beneficial effects in terms of improvement in hepatic steatosis, oxidative stress, and insulin resistance in patients with NAFLD. However, δ-tocotrienol was more potent than α-tocopherol in reducing body weight, inflammation, and apoptosis associated with NAFLD. Trial RegistrationSri Lankan Clinical Trials Registry (https://slctr.lk/SLCTR/2019/038).

Medicinal Formula Huazhi-Rougan Attenuates Non-Alcoholic Steatohepatitis Through Enhancing Fecal Bile Acid Excretion in Mice.

Huazhi-Rougan (HZRG) formula is a Traditional Chinese medicine prescription, and has been widely used to treat non-alcoholic fatty liver disease (NAFLD) and its progressive form non-alcoholic steatohepatitis (NASH). However, the anti-NASH effects and the underlying mechanisms of HZRG have not yet been characterized. Here we showed that 4-week HZRG treatment alleviated methionine-choline-deficiency (MCD) diet-induced NASH in C57BL/6J mice, as evidenced by the improvement of hepatic steatosis and inflammation, as well as the decrease of serum levels of alanine and aspartate transaminases. Fecal 16S rDNA sequencing indicated that HZRG reduced the enrichment of pathogenic bacteria and increased the abundance of bacteria gena that are involved in bile acid (BA) conversation. The alteration of fecal and serum BA profile suggested that HZRG enhanced fecal BA excretion, and reduced the reabsorption of toxic secondary BA species (LCA, DCA, HCA). We further analyzed the BA receptors and transporters, and found that HZRG inhibited the expression of ileal bile acid transporter, and organic solute transporter subunit β, and increased the expression of intestinal tight junction proteins (ZO-1, Occludin, Claudin-2). The modulation of gut dysbiosis and BA profile, as well as the improvement of the intestinal environment, may contribute to the decrease of the p-65 subunit of NF-κB phosphorylation, liver F4/80 positive macrophages, inflammatory cytokine IL-1β and TNF-α expression. In conclusion, HZRG treatment enhances fecal BA excretion via inhibiting BA transporters, modulates BA profiles, gut dysbiosis as well as the intestinal environment, thus contributing to the beneficial effect of HZRG on NASH mice.

Prospective Multicenter Study of the Primary Obesity Surgery Endoluminal (POSE 2.0) Procedure for Treatment of Obesity

The Primary Obesity Surgery Endoluminal (POSE) 2.0 procedure involves a novel pattern of full-thickness gastric body plications to shorten and narrow the stomach using durable suture anchor pairs. Our prospective, multicenter trial examined the safety, efficacy, durability, and physiologic effects of POSE 2.0 in adults with obesity. Adults with obesity underwent POSE 2.0 at 3 centers. Primary outcomes were percent total body weight loss (%TBWL) and proportion of patients achieving >5% TBWL at 12 months. Secondary outcomes included change in obesity comorbidities, satiety, quality of life at 6 months, and durability of plications at 12 and 24 months. Subjects were followed for adverse events throughout the study duration. 44 patients (61% female; mean age, 45 ± 9.7 years; mean body mass index, 37 ± 2.1 kg/m2) were enrolled. This procedure used an average of 19 suture anchor pairs, with a mean duration of 37 ± 11 minutes, and was technically successful in all subjects. Mean %TBWL at 12 months was 15.7% ± 6.8%. At 12 months, %TBWL >5%, >10%, and >15% was achieved in 98%, 86%, and 58% of patients, respectively. Improvements in lipid profile, liver biochemistries, and hepatic steatosis were seen at 6 months. Improvements in hepatic steatosis persisted for 24 months in a subgroup of patients (P < .01). POSE 2.0 reduced maximum tolerated meal volume (P= .03) and was associated with increased fullness (P < .01) and improved eating behavior (P < .01) at 6 months. Impact of weight on quality-of-life questionnaire improved at 6 months (2.23 vs 1.23; P < .01). Repeat assessment at 24 months (n= 26) showed fully intact plications. No serious adverse events occurred. POSE 2.0 is an effective and durable endoscopic bariatric therapy which may influence physiologic pathways impacting satiety. Larger comparative studies are needed to further elucidate these initial findings. gov Identifier: NCT03721731.