p38{gamma} and p38{delta} reprogram liver metabolism by modulating neutrophil infiltration

Non-alcoholic fatty liver disease (NAFLD) is a major health problem and the main cause of liver disease in Western countries. Although NAFLD is strongly associated with obesity and insulin resistance, its pathogenesis remains poorly understood. The disease begins with an excessive accumulation of triglycerides in the liver, which stimulates an inflammatory response. Alternative p38 mitogen-activated kinases (p38 and p38) have been shown to contribute to inflammation in different diseases. Here we demonstrate that p38 is elevated in livers of obese patients with NAFLD and that mice lacking p38/ in myeloid cells are resistant to diet-induced fatty liver, hepatic triglyceride accumulation and glucose intolerance. This protective effect is due to defective migration of p38/-deficient neutrophils to the damaged liver. We further show that neutrophil infiltration in wild-type mice contributes to steatosis development by means of inflammation and liver metabolic changes. Therefore, p38 and p38 in myeloid cells provide a potential target for NAFLD therapy.
Source: EMBO Journal - Category: Molecular Biology Authors: Tags: Immunology, Metabolism, Molecular Biology of Disease Articles Source Type: research

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AbstractNon-alcoholic fatty liver disease (NAFLD) is the most common liver disease which may progress to non-alcoholic steatohepatitis. The prevalence of sarcopenia, which is the loss of muscle mass and strength, is increasing in the aging society. Recent studies reported the relationship between NAFLD and sarcopenia. The skeletal muscle is the primary organ for glucose disposal. Loss of muscle mass can cause insulin resistance, which is an important risk factor for NAFLD. Moreover, obesity, chronic low-grade inflammation, vitamin D deficiency, physical inactivity, hepatokines, and myokines might be involved in the pathoph...
Source: Hepatology International - Category: Infectious Diseases Source Type: research
Non-alcoholic fatty liver disease (NAFLD) is currently the most common chronic liver disease worldwide, affecting 25 –30% of the general population [1], with its prevalence reaching 55% in patients with type 2 diabetes mellitus (T2DM) [2] or even 90% in morbidly obese individuals [3]. NAFLD is characterized by fat accumulation in ≥5% of the hepatocytes, in the absence of excessive alcohol consumption or other secondary causes of liver diseases [4,5]. At the early stages of NAFLD, there is only liver steatosis (i.e.
Source: Metabolism - Clinical and Experimental - Category: Biomedical Science Authors: Source Type: research
This article reviews the most updated information about NAFLD-related HCC and provides some insight into strategies that must be considered to reduce its potential disease burden.
Source: Hepatology International - Category: Infectious Diseases Source Type: research
This study aimed to evaluate whether the CLD prevalence changed between 1998-2001 and 2016-2017. Data were extracted from the Korea National Health and Nutrition Examination Survey (1998-2001 to 2016-2017; n=25,893). Non-alcoholic fatty liver disease (NAFLD) was defined as a hepatic steatosis index>36 in the absence of any other evidence of CLD. The definition of alcoholrelated liver disease (ALD) was excessive alcohol consumption (≥210 g/week for men and ≥140 g/week for women) and an ALD/NAFLD index>0. The prevalence of NAFLD increased from 18.6% (95% confidence interval [CI], 17.8-19.5%) in 1998-2001 to 21.5%...
Source: Clinical and molecular hepatology - Category: Gastroenterology Tags: Clin Mol Hepatol Source Type: research
AbstractPurpose of ReviewThis review summarizes our current understanding of the metabolic syndrome (MetS) in children and adolescents. Special emphasis is given towards diagnostic criteria and therapeutic options.Recent FindingsConsistent diagnostic criteria to define MetS in childhood and adolescence are not available to date. There is common agreement that the main features defining MetS include (1) disturbed glucose metabolism, (2) arterial hypertension, (3) dyslipidemia, and (4) abdominal obesity. However, settings of cut-off values are still heterogeneous in the pediatric population. Additional features that may defi...
Source: Current Obesity Reports - Category: Eating Disorders & Weight Management Source Type: research
Obesity and dyslipidemia are major risk factors associated with non-alcoholic fatty liver disease (NAFLD). NAFLD refers to the accumulation of fat in more than 5% of the liver without alcohol consumption. NAFL...
Source: BMC Complementary and Alternative Medicine - Category: Complementary Medicine Authors: Tags: Research article Source Type: research
The objective of the present study was to gain deeper knowledge about the metabolic processes involved in the NASH animal model, and particularly in the effect of PH by using metabolomics. For achieving such information, twelve 8-week-old male C57BL/6 J mice, fed commercial chow (control diet) or methionine and choline-Deficient diet (MCD) for three weeks were subjected to PH and sacrificed 2 weeks later. Livers were removed and submitted to metabolic profiling analysis through RP-LC/MS (qTOF), GC/MS (qTOF) and CE/MS(TOF). More than 3000 different features were detected and repeated measurements one-way ANOVA analys...
Source: Journal of Pharmaceutical and Biomedical Analysis - Category: Drugs & Pharmacology Source Type: research
ConclusionThese findings indicate that CPT may exert the therapeutic effects on NAFLD via regulating PI3K/Akt/GSK3β pathway.Graphical Abstract
Source: Phytomedicine - Category: Drugs & Pharmacology Source Type: research
This study demonstrated that amlexanox reversed glucose and lipid metabolic disturbance and hepatic steatosis in NAFLD mice model. IKKε was specific expressed in hepatic stellate cells (HSCs) instead of hepatocytes. This study also found that amlexanox improved insulin signaling (Insulin-IRS-1-Akt) in hepatocytes through inhibiting inflammation (IKKε-NF-κB-TNF-α/IL-1α) in HSCs.SignificanceThe present study confirmed that IKKε was specific expressed in HSCs. Inhibition of activated HSCs was responsible for effects of amlexanox on NAFLD, with improving insulin signal pathway in hepatocytes.
Source: Life Sciences - Category: Biology Source Type: research
(Natural News) Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease today. Fatty liver is commonly caused by excessive alcohol intake. However, as its name implies, NAFLD can develop with little to no alcohol consumption. New research published in the journal BMC Complementary and Alternative Medicine suggested that people with NAFLD may benefit...
Source: NaturalNews.com - Category: Consumer Health News Source Type: news
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