• adolescence
• insulin resistance
• obesity
• overweight
• type 2 diabetes mellitus

• Humans
• Insulin Resistance
• Male
• Female
• Child
• Adolescent
• Pediatric Obesity/blood
• Overweight/blood
• Body Mass Index
• Triglycerides/blood
• Cholesterol, HDL/blood
• Blood Glucose/analysis
• Blood Glucose/metabolism
• Biomarkers/blood

• Glucagon-like peptide-1
• glucagon-like peptide-1 receptor agonist
• insulin resistance
• non-alcoholic fatty liver disease
• non-alcoholic steatohepatitis
• steatosis.

• Humans
• Non-alcoholic Fatty Liver Disease/drug therapy
• Glucagon-Like Peptide 1/pharmacology
• Glucagon-Like Peptide 1/physiology
• Glucagon/therapeutic use
• Blood Glucose
• Insulin Secretion
• Glucagon-Like Peptide-1 Receptor
• Diabetes Mellitus, Type 2/drug therapy
• Hypoglycemic Agents/therapeutic use

• ketogenesis
• ketone
• metabolic-associated fatty liver disease

• Humans
• Non-alcoholic Fatty Liver Disease
• Fatty Acids

• biomarker
• diabetic kidney disease
• metabolic-associated fatty liver disease

• cohort study
• nonalcoholic fatty liver disease
• risk factor
• type 2 diabetes
• visceral fat obesity

• National Key Research and Development Program of China

• rehabilitation
• liver

• Adult
• Humans
• Male
• Alanine Transaminase
• Athletes
• Liver
• Bilirubin
• Aspartate Aminotransferases

• NAFLD
• lean
• nonalcoholic fatty liver disease
• obesity
• risk of diabetes

• China
• T2DM
• cohort study
• new Chinese diabetes risk score
• screening

• Humans
• China/epidemiology
• Cohort Studies
• Diabetes Mellitus, Type 2/diagnosis
• Diabetes Mellitus, Type 2/epidemiology
• East Asian People
• Risk Factors

• Sanming Project of Medicine in Shenzhen
• Science and Technology Planning Project of Shenzhen Municipality
• Natural Science Foundation of Guangdong Province

• Acetylated polysaccharides
• NAFLD
• Nrf2/JNK1/AMPK pathways
• Stropharia rugoso-annulata

Metabolic fatty liver disease caused by high-starch diet restricted the intensive and sustainable development of carnivorous fish such as largemouth bass. In this study, the combination liver proteomic and lipidomic approach was employed to investigate the key signaling pathways and identify the critical biomarkers of fatty liver in largemouth bass. Joint analysis of the correlated differential proteins and lipids revealed nine common metabolic pathways; it was determined that FABP1 were significantly up-regulated in terms of transporting more triglycerides into the liver, while ABCA1 and VDAC1 proteins were significantly down-regulated in terms of preventing the transport of lipids and cholesterol out of the liver, leading to triglyceride accumulation in hepatocyte, eventually resulting in metabolic fatty liver disease. The results indicate that FABP1, ABCA1 and VDAC1 could be potential biomarkers for treating metabolic fatty liver disease of largemouth bass.

• Alanine aminotransferase
• Alkaline phosphatase
• Aspartate amino-transferase
• Diabetes
• Liver enzymes
• Prospective epidemiological research studies in IrAN
• Y-glutamyltransferase

• Adult
• Alanine Transaminase
• Aspartate Aminotransferases
• Cohort Studies
• Cross-Sectional Studies
• Diabetes Mellitus/epidemiology
• Humans
• Liver
• Prospective Studies
• gamma-Glutamyltransferase

As a common chronic metabolic disease, the development of diabetes mellitus (DM) may also be accompanied by liver damage and inflammatory disorders. Sitagliptin is an inhibitor of dipeptidyl peptidase-4 (DPP4, also known as CD26), which is clinically used for DM treatment. However, the mechanism of sitagliptin’s efficiency in liver diseases is largely unknown. In this study, mice suffering from streptozotocin (STZ) exhibit elevated liver DPP4 expression and activity, as well as inflammatory and chronic liver injury phenotype, whereas specifically inhibiting the activity of DPP4 in mouse liver tissues and hepatocytes by sitagliptin contributes to decreased cytokines, oxidative stress, cell apoptosis, and inflammation in STZ-induced diabetic mice. Moreover, sitagliptin reduced TNFα or LPS-induced cellular reactive oxygen species (ROS) level, cell apoptosis, and protein expression in the NFκB signaling pathway in HepG2 cells or primary mouse hepatocytes. Altogether, our study confirms that sitagliptin may protect liver tissue by alleviating ROS production and NFκB signaling activation, providing a putative mechanism for preventing the development of diabetic liver disease.

Nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) may be linked to development of chronic kidney diseases (CKD). The FIB4 index, a noninvasive liver fibrosis score, has been reported to predict CKD in non-diabetic patients, but there are no reports yet in diabetic cases. Therefore, we evaluated the prognostic impact of FIB4 index on the risk of developing diabetic kidney disease (DKD) in Japanese patients with type 2 diabetes in a retrospective cohort study. We assessed patients with type 2 diabetes with an eGFR ≥ 60 mL/min/1.73 m² and without dipstick positive proteinuria (≥ 1 +) at their first visit to our department. Participants were divided into two groups based on the FIB4 index at their first visit: FIB4 index > 1.3 and FIB4 index ≤ 1.3. The primary endpoint was defined as a decrease in eGFR < 60 mL/min/1.73 m² or the onset of proteinuria during the course of treatment. The average age of all 584 type 2 diabetic participants (360 [61.6%] men) was 55 ± 11 years. There were 187 patients in the FIB4 index group > 1.3 (32.0%) and the median observation period was 6.0 (3.8–11.0) years. Kaplan–Meier survival analysis indicated that the risks of developing DKD, eGFR < 60 and proteinuria were all higher in FIB4 index > 1.3 patients than in FIB4 ≤ 1.3 patients. In the Cox regression analysis, an FIB4 index > 1.3 was a significant predictor for onset of DKD (HR 1.54, 95% CI 1.15–2.08) and proteinuria (HR 1.55, 95% CI 1.08–2.23), but not for an eGFR < 60 (HR 1.14, 95% CI 0.79–1.99). To the best of our knowledge, this is the first study to demonstrate that an FIB4 index > 1.3 has a prognostic impact on the development of CKD and proteinuria in type 2 diabetic patients. This warrants further investigation of the prognostic impact of the development of DKD or proteinuria.

• Immune cells
• Immunology
• Immunotherapy
• Lipid nanoparticles
• Liver fiibrosis
• Macrophages
• Microfluidic mixing
• Monocytes
• Nanomedicines
• Nanotechnology
• Nucleic acid therapeutics
• Obesity
• Reticuloendothelial cells
• T cells

• hepatic steatosis
• macrophage infiltration
• mesangial expansion
• obesity
• ovariectomy

• Alanine aminotransferase
• Diabetes mellitus
• Gamma-glutamyl transferase
• Non-obesity
• Obesity

• CVD
• Complications
• Epidemiology
• Mortality
• NAFLD
• NASH
• T2DM

• Cardiovascular Diseases/etiology
• Diabetes Mellitus, Type 2/etiology
• Humans
• Liver/pathology
• Liver Transplantation/methods
• Morbidity
• Non-alcoholic Fatty Liver Disease/complications
• Non-alcoholic Fatty Liver Disease/mortality
• Prevalence

• Department of Health

Despite recent advancements in clinical drugs, diabetes treatment still needs further progress. As such, ongoing research has attempted to determine the precise molecular mechanisms of the disorder. Specifically, evidence supports that several signaling pathways play pivotal roles in the development of diabetes. However, the exact molecular mechanisms of diabetes still need to be explored. This study examines exciting new hallmarks for the strict involvement of autophagy and TGF-β signaling pathways in the pathogenesis of diabetes and the design of novel therapeutic strategies. Dysregulated autophagy in pancreatic β cells due to hyperglycemia, oxidative stress, and inflammation is associated with diabetes and accompanied by dysregulated autophagy in insulin target tissues and the progression of diabetic complications. Consequently, several therapeutic agents such as adiponectin, ezetimibe, GABA tea, geniposide, liraglutide, guava extract, and vitamin D were shown to inhibit diabetes and its complications through modulation of the autophagy pathway. Another pathway, TGF-β signaling pathway, appears to play a part in the progression of diabetes, insulin resistance, and autoimmunity in both type 1 and 2 diabetes and complications in diabetes. Subsequently, drugs that target TGF-β signaling, especially naturally derived ones such as resveratrol, puerarin, curcumin, hesperidin, and silymarin, as well as Propolis, Lycopus lucidus, and Momordica charantia extracts, may become promising alternatives to current drugs in diabetes treatment. This review provides keen insights into novel therapeutic strategies for the medical care of diabetes.

• TGF-β
• autophagy
• diabetes
• natural agents
• systematic review

• Hepatic insulin resistance
• Molecular mechanism
• Nonalcoholic fatty liver disease
• Treatment strategy

• Adipose tissue
• CKD
• Dysbiosis
• Gut microbiota
• Insulin resistance
• Metabolic syndrome
• Non-alcoholic fatty liver disease
• Type 2 diabetes

This study was performed to evaluate the efficacy of metformin on liver fat content (LFC) in first episode schizophrenia patients with olanzapine-induced weight gain, and the relationship between the change of LFC and the other metabolic indices.

In a double-blind study, the clinically stable inpatients with first-episode schizophrenia under olanzapine monotherapy who gained more than 7% of their baseline weight were randomly assigned to two groups; one with olanzapine plus metformin (1,000 mg/day) (metformin group) and the other with olanzapine plus placebo (placebo group) for 16 weeks. All patients continued to maintain the original olanzapine dosage. LFC was measured by magnetic resonance imaging at baseline and at the end of 16 weeks, respectively. At the same time, glucose and lipid metabolism, homeostasis model assessment of insulin resistance index (HOMA-IR) were measured respectively, analyzing the correlation between the change value of LFC and other indicators.

Over the 16-week study period, LFC value in metformin group decreased compared with baseline. LFC change across the 16-week treatment period was −2.91% for the metformin group and 0.59% for the placebo group, with a between-group difference of −3.5% (95% confidence interval, −6.08 to −0.93; p = 0.009). Compared to baseline, in the metformin group, triglyceride and HOMA-IR reduced significantly, while high density lipoprotein cholesterol increased significantly at weeks 16. There was positive correlation between LFC changes and triglycerides, HOMA-IR changes significantly.

Metformin can significantly attenuate LFC in schizophrenia patients with olanzapine-induced weight gain. It may be related to the improvement of the part of the glucolipid metabolic indices.

• Insulin resistance
• Liver fat.
• Metabolic syndrome
• Metformin
• Olanzapine
• Schizophrenia

• NAFLD
• NASH
• diabetes
• liver
• obesity

• chemical shift encoded MRI
• diurnal variation
• hepatic steatosis
• magnetic resonance imaging
• proton density fat fraction
• repeatability
• reproducibility

• anti-diabetic drug
• drug mechanism
• fatty
• glucose metabolism
• insulin resistance
• liver

• Animals
• Diabetes Mellitus, Type 2/drug therapy
• Diabetes Mellitus, Type 2/metabolism
• Fatty Acids/metabolism
• Humans
• Hypoglycemic Agents/pharmacology
• Hypoglycemic Agents/therapeutic use
• Lipid Metabolism/drug effects
• Lipogenesis/drug effects
• Liver/drug effects
• Liver/metabolism
• Metformin/pharmacology
• Metformin/therapeutic use
• Mice
• Non-alcoholic Fatty Liver Disease/drug therapy
• Non-alcoholic Fatty Liver Disease/metabolism
• Oxidation-Reduction/drug effects
• Rats
• Triglycerides/metabolism

• FS/15/56/31645 British Heart Foundation
• MR/P011462/1 Medical Research Council

• Adult
• Case-Control Studies
• Diabetes Mellitus, Type 2/physiopathology
• Female
• Follow-Up Studies
• Humans
• Male
• Middle Aged
• Non-alcoholic Fatty Liver Disease/epidemiology
• Non-alcoholic Fatty Liver Disease/pathology
• Prevalence
• Prognosis
• Sri Lanka/epidemiology
• Young Adult

• Cardiovascular risk markers
• Carotid intima-media thickness
• Fatty liver disease
• NAFLD and diabetes
• NAFLD screening process
• Surrogate markers of cardiovascular disease

• Biomarkers
• Cardiovascular Diseases/etiology
• Carotid Intima-Media Thickness
• Disease Progression
• Humans
• Non-alcoholic Fatty Liver Disease/complications
• Risk Factors

• Akt
• FAM3 gene family
• Insulin resistance
• NAFLD
• Type 2 diabetes

• Animals
• Cytokines/blood
• Cytokines/physiology
• Diabetes Mellitus, Type 2/etiology
• Diabetes Mellitus, Type 2/metabolism
• Glucose/metabolism
• Humans
• Insulin Resistance
• Lipid Metabolism
• Liver/metabolism
• Neoplasm Proteins/blood
• Non-alcoholic Fatty Liver Disease/etiology
• Non-alcoholic Fatty Liver Disease/metabolism
• PPAR gamma/physiology
• Signal Transduction

• Adolescent
• Adult
• Disease Progression
• Female
• Glomerular Filtration Rate
• Humans
• Longitudinal Studies
• Male
• Middle Aged
• Non-alcoholic Fatty Liver Disease/complications
• Proteinuria/etiology
• Proteinuria/pathology
• Renal Insufficiency, Chronic/etiology
• Renal Insufficiency, Chronic/pathology
• Retrospective Studies
• Risk Factors
• Severity of Illness Index
• Young Adult

Globally, steatosis is the commonest type of liver pathology and is closely associated with obesity and the metabolic syndrome. Obesity is common in urban African females but no data is available on hepatic fat content in this population group when compared to other ethnic groups. The aim of this study was therefore to compare hepatic fat content in woman from different ethnic groups in South Africa and to characterise the principle determinants of liver fat.

A convenience sample of 106 (48 Indian, 29 African and 29 Caucasian) female volunteers aged 20–60 years and having no history of cardiometabolic disorders were recruited. Hepatic fat was determined from CT scans using the liver-spleen attenuation ratio (LAR), which decreases with increasing levels of hepatic fat. Anthropometric and cardiometabolic parameters were measured with insulin resistance determined using the HOMA index and dysglycaemia defined as fasting glucose ≥5.60 mmol/L.

The African subjects had significantly lower hepatic fat content (LAR as median [interquartile range]: 1.35 [1.28, 1.41]) than the Indian (1.22 [1.10, 1.35]; p<0.005) and Caucasian (1.27 [1.16, 1.33]; p<0.05) females even though they had significantly higher BMIs than both groups (p<0.0005 and p<0.05, respectively). Linear regression showed that: subcutaneous abdominal fat was a significant (unstandardised β = 0.007; p = 0.03) negative, whilst insulin resistance (β = -0.97; p = 0.01) and dysglycaemia (β = -3.58; p = 0.01) were significant positive determinants of liver fat; higher hepatic fat levels in subjects with the metabolic syndrome were explained by insulin resistance and dysglycaemia.

African ethnicity is associated with low liver fat content. Subcutaneous abdominal fat protects against steatosis, possibly by acting as a triglyceride reservoir. Insulin resistance and dysglycaemia lead to greater hepatic fat deposition and explain higher liver fat levels in subjects with the metabolic syndrome. These observations must be further investigated in longitudinal surveys.

The liver is a principal metabolic organ within the human body and has a major role in regulating carbohydrate, fat, and protein metabolism. With increasing rates of obesity, the prevalence of non-alcoholic fatty liver disease (NAFLD) is growing. It remains unclear why NAFLD, which is now defined as the hepatic manifestation of the metabolic syndrome, develops but lifestyle factors such as diet (ie, total calorie and specific nutrient intakes), appear to play a key role. Here we review the available observational and intervention studies that have investigated the influence of dietary macronutrients on liver fat content. Findings from observational studies are conflicting with some reporting that relative to healthy controls, patients with NAFLD consume diets higher in total fat/saturated fatty acids, whilst others find they consume diets higher in carbohydrates/sugars. From the limited number of intervention studies that have been undertaken, a consistent finding is a hypercaloric diet, regardless of whether the excess calories have been provided either as fat, sugar, or both, increases liver fat content. In contrast, a hypocaloric diet decreases liver fat content. Findings from both hyper- and hypo-caloric feeding studies provide some suggestion that macronutrient composition may also play a role in regulating liver fat content and this is supported by data from isocaloric feeding studies; fatty acid composition and/or carbohydrate content/type appear to influence whether there is accrual of liver fat or not. The mechanisms by which specific macronutrients, when consumed as part of an isocaloric diet, cause a change in liver fat remain to be fully elucidated.

• NAFLD
• carbohydrate
• diet
• fat
• human
• liver
• protein

• Endocrinology
• Metabolism

Treatment of subjects with non-alcoholic fatty liver disease (NAFLD) with omega-3 polyunsaturated fatty acids (FAs) suggests high levels of docosahexaenoic acid (DHA) tissue enrichment decrease liver fat content. We assessed whether changes in erythrocyte DHA enrichment (as a surrogate marker of changes in tissue enrichment) were associated with alterations in hepatic de novo lipogenesis (DNL), postprandial FA partitioning and hepatic and peripheral insulin sensitivity in a sub-study of the WELCOME trial (Wessex Evaluation of fatty Liver and Cardiovascular markers in NAFLD (non-alcoholic fatty liver disease) with OMacor thErapy).

Sixteen participants were randomised to 4 g/day EPA+DHA (n=8) or placebo (n=8) for 15–18 months and underwent pre- and post-intervention measurements. Fasting and postprandial hepatic FA metabolism was assessed using metabolic substrates labelled with stable-isotope tracers (²H₂O and [U¹³C]palmitate). Insulin sensitivity was measured by a stepped hyperinsulinaemic-euglycaemic clamp using deuterated glucose. Participants were stratified according to change in DHA erythrocyte enrichment (< or ⩾2% post intervention).

Nine participants were stratified to DHA⩾2% (eight randomised to EPA+DHA and one to placebo) and seven to the DHA<2% group (all placebo). Compared with individuals with erythrocyte <2% change in DHA abundance, those with ⩾2% enrichment had significant improvements in hepatic insulin sensitivity, reduced fasting and postprandial plasma triglyceride concentrations, decreased fasting hepatic DNL, as well as greater appearance of ¹³C from dietary fat into plasma 3-hydroxybutyrate (all P<0.05).

The findings from our pilot study indicate that individuals who achieved a change in erythrocyte DHA enrichment ⩾2% show favourable changes in hepatic FA metabolism and insulin sensitivity, which may contribute to decreasing hepatic fat content.

Combatting over-weight or obesity can lead to large fluctuations in an individual’s body weight, often referred to as weight cycling or “yo-yo” dieting. Current evidence regarding the potentially damaging effects of these changes is conflicting.

Here, we assess the metabolic effects of weight cycling in a murine model, comprising three dietary switches to normal or high fat diets at 6 week intervals; male C57BL/6 mice were fed either a control (C) or high fat (F) diet for 6 weeks (n=140/group). C and F groups were then either maintained on their initial diet (CC and FF respectively) or switched to a high fat (CF) or control (FC) diet (n=35/group). For the final 6 week interval, CC and CF groups were returned to the control diet (CCC and CFC groups) while FC and FF groups were placed on a high fat diet (FCF and FFF) (n=28/group).

For the majority of metabolic outcomes changes aligned with dietary switches; however assessment of neuropeptides and receptors involved in appetite regulation and reward signalling pathways reveal variable patterns of expression. Furthermore, we demonstrate that multiple cycling events leads to a significant increase in internal fat deposition, even when compared to animals maintained on a high fat diet (Internal Fat: FCF: 7.4 ± 0.2g vs. FFF: 5.6 ± 0.2g; p<0.01).

Increased internal adipose tissue is strongly linked to the development of metabolic syndrome associated conditions such as type 2 diabetes, cardiovascular disease and hypertension. While further work will be required to elucidate the mechanisms underlying the neuronal control of energy homeostasis, these studies provide a causative link between weight cycling and adverse health.

• Diabetes risk
• Epidemiology
• NAFLD
• Non-alcoholic fatty liver disease
• Type 2 diabetes

• Adult
• Aged
• Aged, 80 and over
• Alanine Transaminase/blood
• Biomarkers/blood
• C-Reactive Protein/metabolism
• Case-Control Studies
• Diabetes Mellitus, Type 2/blood
• Diabetes Mellitus, Type 2/epidemiology
• Female
• Ferritins/blood
• Ferritins/metabolism
• Follow-Up Studies
• Humans
• Incidence
• Iron/blood
• Iron/metabolism
• Male
• Middle Aged
• Multivariate Analysis
• Proportional Hazards Models
• Prospective Studies
• Risk Factors
• Transferrin/metabolism
• Young Adult
• gamma-Glutamyltransferase/blood

• MR/L003120/1 Medical Research Council
• MC_UP_A100_1003 Medical Research Council
• 097451 Wellcome Trust
• RG/08/014/24067 British Heart Foundation
• 16491 Cancer Research UK
• Wellcome Trust
• MC_UU_12015/5 Medical Research Council
• 001 World Health Organization
• G0800270 Medical Research Council
• MC_UU_12015/1 Medical Research Council

• cohort study
• diabetes
• epidemiology
• liver disease
• non-alcoholic fatty liver

• C. sativus
• Cucumber
• Diabetes complications
• Glycation
• Hepatoprotection
• Liver

• Dyslipidaemia
• Metabolic syndrome
• NAFLD
• Obesity
• Type 2 diabetes mellitus

• Age Factors
• Diabetes Mellitus, Type 2/complications
• Ethnicity
• Humans
• Hyperlipidemias/complications
• Hypertension/complications
• Metabolic Syndrome/complications
• Non-alcoholic Fatty Liver Disease/epidemiology
• Non-alcoholic Fatty Liver Disease/genetics
• Obesity/complications
• Risk Factors
• Sex Factors

• Docosahexaenoic acid
• eicosapentaenoic acid
• non-alcoholic fatty liver disease
• non-alcoholic steatohepatitis
• omega-3