Huazhi Rougan Granules attenuates steatosis in cell model of nonalcoholic fatty liver disease by inducing autophagy / 中国中药杂志

To investigate the effect of Huazhi Rougan Granules(HZRG) on autophagy in a steatotic hepatocyte model of free fatty acid(FFA)-induced nonalcoholic fatty liver disease(NAFLD) and explore the possible mechanism. FFA solution prepared by mixing palmitic acid(PA) and oleic acid(OA) at the ratio of 1∶2 was used to induce hepatic steatosis in L02 cells after 24 h treatment, and an in vitro NAFLD cell model was established. After termination of incubation, cell counting kit-8(CCK-8) assay was performed to detect the cell viability; Oil red O staining was employed to detect the intracellular lipid accumulation; enzyme-linked immunosorbnent assay(ELISA) was performed to measure the level of triglyceride(TG); to monitor autophagy in L02 cells, transmission electron microscopy(TEM) was used to observe the autophagosomes; LysoBrite Red was used to detect the pH change in lysosome; transfection with mRFP-GFP-LC3 adenovirus was conducted to observe the autophagic flux; Western blot was performed to determine the expression of autophagy marker LC3B-Ⅰ/LC3B-Ⅱ, autophagy substrate p62 and silent information regulator 1(SIRT1)/adenosine 5'-monophosphate(AMP)-activated protein kinase(AMPK) signaling pathway. NAFLD cell model was successfully induced by FFA at 0.2 mmol·L~(-1) PA and 0.4 mmol·L~(-1) OA. HZRG reduced the TG level(P<0.05, P<0.01) and the lipid accumulation of FFA-induced L02 cells, while elevated the number of autophagosomes and autophagolysosomes to generate autophagic flux. It also affected the functions of lysosomes by regulating their pH. Additionally, HZRG up-regulated the expression of LC3B-Ⅱ/LC3B-Ⅰ, SIRT1, p-AMPK and phospho-protein kinase A(p-PKA)(P<0.05, P<0.01), while down-regulated the expression of p62(P<0.01). Furthermore, 3-methyladenine(3-MA) or chloroquine(CQ) treatment obviously inhibited the above effects of HZRG. HZRG prevented FFA-induced steatosis in L02 cells, and its mechanism might be related to promoting autophagy and regulating SIRT1/AMPK signaling pathway.

Effect of diosgenin on mTOR/FASN/HIF-1α/VEGFA expression in rats with non-alcoholic fatty liver disease / 中国中药杂志

The present study aimed to investigate the effect of diosgenin on mammalian target of rapamycin(mTOR), fatty acid synthase(FASN), hypoxia inducible factor-1α(HIF-1α), and vascular endothelial growth factor A(VEGFA) expression in liver tissues of rats with non-alcoholic fatty liver disease(NAFLD) and explore the mechanism of diosgenin on lipogenesis and inflammation in NAFLD. Forty male SD rats were divided into a normal group(n=8) fed on the normal diet and an experimental group(n=32) fed on the high-fat diet(HFD) for the induction of the NAFLD model. After modeling, the rats in the experimental group were randomly divided into an HFD group, a low-dose diosgenin group(150 mg·kg~(-1)·d~(-1)), a high-dose diosgenin group(300 mg·kg~(-1)·d~(-1)), and a simvastatin group(4 mg·kg~(-1)·d~(-1)), with eight rats in each group. The drugs were continuously given by gavage for eight weeks. The levels of triglyceride(TG), total cholesterol(TC), low-density lipoprotein cholesterol(LDL-C), alanine transaminase(ALT), and aspartate transaminase(AST) in the serum were detected by the biochemical method. The content of TG and TC in the liver was detected by the enzyme method. Enzyme-linked immunosorbent assay(ELISA) was used to measure interleukin 1β(IL-1β) and tumor necrosis factor α(TNF-α) in the serum. Lipid accumulation in the liver was detected by oil red O staining. Pathological changes of liver tissues were detected by hematoxylin-eosin(HE) staining. The mRNA and protein expression levels of mTOR, FASN, HIF-1α, and VEGFA in the liver of rats were detected by real-time fluorescence-based quantitative polymerase chain reaction(PCR) and Western blot, respectively. Compared with the normal group, the HFD group showed elevated body weight and levels of TG, TC, LDL-C, ALT, AST, IL-1β, and TNF-α(P<0.01), increased lipid accumulation in the liver(P<0.01), obvious liver steatosis, up-regulated mRNA expression levels of mTOR, FASN, HIF-1α, and VEGFA(P<0.01), and increased protein expression levels of p-mTOR, FASN, HIF-1α, and VEGFA(P<0.01). Compared with the HFD group, the groups with drug treatment showed lowered body weight and levels of TG, TC, LDL-C, ALT, AST, IL-1β, and TNF-α(P<0.05, P<0.01), reduced lipid accumulation in the liver(P<0.01), improved liver steatosis, decreased mRNA expression levels of mTOR, FASN, HIF-1α, and VEGFA(P<0.05, P<0.01), and declining protein expression levels of p-mTOR, FASN, HIF-1α, and VEGFA(P<0.01). The therapeutic effect of the high-dose diosgenin group was superior to that of the low-dose diosgenin group and the simvastatin group. Diosgenin may reduce liver lipid synthesis and inflammation and potentiate by down-regulating the mTOR, FASN, HIF-1α, and VEGFA expression, playing an active role in preventing and treating NAFLD.

Therapeutic potential of alkaloid extract from Codonopsis Radix in alleviating hepatic lipid accumulation: insights into mitochondrial energy metabolism and endoplasmic reticulum stress regulation in NAFLD mice / 中国天然药物

Alkaloids are a class of naturally occurring bioactive compounds that are widely distributed in various food sources and Traditional Chinese Medicine. This study aimed to investigate the therapeutic effects and underlying mechanisms of alkaloid extract from Codonopsis Radix (ACR) in ameliorating hepatic lipid accumulation in a mouse model of non-alcoholic fatty liver disease (NAFLD) induced by a high-fat diet (HFD). The results revealed that ACR treatment effectively mitigated the abnormal weight gain and hepatic injury associated with HFD. Furthermore, ACR ameliorated the dysregulated lipid metabolism in NAFLD mice, as evidenced by reductions in serum triglyceride, total cholesterol, and low-density lipoprotein levels, accompanied by a concomitant increase in the high-density lipoprotein level. ACR treatment also demonstrated a profound anti-oxidative effect, effectively alleviating HFD-induced oxidative stress and promoting ATP production. These effects were achieved through the up-regulation of the activities of mitochondrial electron transfer chain complexes I, II, IV, and V, in addition to the activation of the AMPK/PGC-1α pathway, suggesting that ACR exhibits therapeutic potential in alleviating the HFD-induced dysregulation of mitochondrial energy metabolism. Moreover, ACR administration mitigated HFD-induced endoplasmic reticulum (ER) stress and suppressed the overexpression of ubiquitin-specific protease 14 (USP14) in NAFLD mice. In summary, the present study provides compelling evidence supporting the hepatoprotective role of ACR in alleviating lipid deposition in NAFLD by improving energy metabolism and reducing oxidative stress and ER stress. These findings warrant further investigation and merit the development of ACR as a potential therapeutic agent for NAFLD.

Nonalcoholic fatty liver disease and bilirubin: correlation, mechanism, and therapeutic perspectives / 中华肝脏病杂志

Non-alcoholic fatty liver disease (NAFLD) is a metabolic-related disorder induced by multiple factors and mainly characterized by excessive fat buildup in hepatocytes. With the consumption of a Western-style diet and obesity prevalence in recent years, the incidence of NAFLD has gradually increased, becoming an increasingly serious public health problem. Bilirubin is a heme metabolite and a potent antioxidant. Studies have demonstrated that bilirubin levels have an inverse correlation with the incidence rate of NAFLD; however, which form of bilirubin plays the main protective role is still controversial. It is considered that the main protective mechanisms for NAFLD are bilirubin antioxidant properties, insulin resistance reduction, and mitochondrial function. This article summarizes the correlation, protective mechanism, and possible clinical application of NAFLD and bilirubin.

Zuogui Jiangtang Qinggan Prescription promotes recovery of intestinal mucosal barrier in mice with type 2 diabetes mellitus and nonalcoholic fatty liver disease by improving intestinal flora homeostasis / 中国中药杂志

This study aimed to investigate the recovery effect of Zuogui Jiangtang Qinggan Prescription on intestinal flora homeostasis control and intestinal mucosal barrier in type 2 diabetes mellitus(T2DM) with nonalcoholic fatty liver disease(NAFLD) induced by a high-fat diet. NAFLD was established in MKR transgenic mice(T2DM mice) by a high-fat diet(HFD), and subsequently treated for 8 weeks with Zuogui Jiangtang Qinggan Prescription(7.5, 15 g·kg~(-1)) and metformin(0.067 g·kg~(-1)). Triglyceride and liver function were assessed using serum. The hematoxylin-eosin(HE) staining and Masson staining were used to stain the liver tissue, while HE staining and AB-PAS staining were used to stain the intestine tissue. 16S rRNA sequencing was utilized to track the changes in the intestinal flora of the mice in each group. Polymerase chain reaction(PCR) and immunofluorescence were used to determine the protein and mRNA expression levels of ZO-1, Occludin, and Claudin-1. The results demonstrated that Zuogui Jiangtang Qinggan Prescription increased the body mass of T2DM mice with NAFLD and decreased the hepatic index. It down-regulated the serum biomarkers of liver function and dyslipidemia such as alanine aminotransferase(ALT), aspartate transaminase(AST), and triglycerides(TG), increased insulin sensitivity, and improved glucose tolerance. According to the results of 16S rRNA sequencing, the Zuogui Jiangtang Qinggan Prescription altered the composition and abundance of the intestinal flora, increasing the relative abundances of Muribaculaceae, Lactobacillaceae, Lactobacillus, Akkermansia, and Bacteroidota and decreasing the relative abundances of Lachnospiraceae, Firmicutes, Deslfobacteria, Proteobacteria, and Desulfovibrionaceae. According to the pathological examination of the intestinal mucosa, Zuogui Jiangtang Qinggan Prescritpion increased the expression levels of the tight junction proteins ZO-1, Occludin, and Claudin-1, promoted intestinal mucosa repair, protected intestinal villi, and increased the height of intestinal mucosa villi and the number of goblet cells. By enhancing intestinal mucosal barrier repair and controlling intestinal microbiota homeostasis, Zuogui Jiangtang Qinggan Prescription reduces intestinal mucosal damage induced by T2DM and NAFLD.

TSPAN8 is involved in lipid metabolism in non-alcoholic fatty liver disease in mice / 南方医科大学学报

OBJECTIVE@#To investigate the changes of tetraspanin 8 (TSPAN8) expression levels and its role in lipid metabolism during the development of non-alcoholic fatty liver disease (NAFLD).@*METHODS@#Thirty male C57BL/6J mice were randomly divided into normal diet group and high-fat diet (HFD) group (n=15), and after feeding for 1, 3, and 6 months, the expression levels of TSPAN8 in the liver tissues of the mice were detected with Western blotting. In a HepG2 cell model of NAFLD induced by free fatty acids (FFA), the effect of TSPAN8 overexpression on lipid accumulation was examined using Oil Red O staining and an automated biochemical analyzer, and the mRNA expressions of the key genes involved in lipid metabolism were detected using qRT-PCR.@*RESULTS@#Western blotting showed that compared with that in mice with normal feeding, the expression of TSPAN8 was significantly decreased in the liver tissues of mice with HFD feeding for 3 and 6 months (P < 0.05). In HepG2 cells, treatment with FFA significantly decreased the expression of TSPAN8 at both the mRNA and protein levels (P < 0.01). TSPAN8 overexpression in FFA-treated cells showed significantly lowered intracellular triglyceride levels (P < 0.001) and obviously reduced mRNA expression of fatty acid transport protein 5 (FATP5) (P < 0.01). The expression of FATP5 was significantly increased in FFA-treated cells as compared with the control cells (P < 0.001).@*CONCLUSION@#TSPAN8 is involved in lipid metabolism in NAFLD, and overexpression of TSPAN8 may inhibit cellular lipid deposition by reducing the expression of FATP5.

Gynostemma pentaphyllum saponins alleviate non-alcoholic fatty liver disease in rats by regulating intestinal flora and short-chain fatty acid metabolism / 中国中药杂志

This study aimed to explore the effects of Gynostemma pentaphyllum saponins(GPs) on non-alcoholic fatty liver disease(NAFLD) induced by high-fat diet in rats and reveal the underlying mechanism. The NAFLD model rats were prepared with high-fat diet. Forty male Sprague Dawley(SD) rats were randomly assigned into the control group, model group, and low-, moderate-, and high-dose GPs(50, 100, and 150 mg·kg~(-1), respectively) groups. After intragastric administration for 8 continuous weeks, we determined the body weight, liver weight, the levels of total cholesterol(TC), triglyceride(TG), low-density lipoprotein cholesterol(LDL-c), high-density lipoprotein cholesterol(HDL-c), alanine aminotransferase(ALT), and aspartate aminotransferase(AST) in serum, and the levels of TC, TG, malondialdehyde(MDA), superoxide dismutase(SOD), catalase(CAT), and interleukin 6(IL-6) in the liver. Furthermore, we observed the pathological changes of liver tissue by oil red O staining and hematoxylin-eosin(HE) staining, sequenced the 16 S rRNA of the intestinal flora in rat feces, and determined the content of short-chain fatty acids in rat feces. The results showed that GPs inhibited the excessive weight gain of high-fat diet-induced NAFLD in rats, reduced the liver weight, lowered the TC, TG, LDL-c, AST, and ALT levels in serum(P<0.05), and rose the HDL-c level in serum(P<0.01). GPs relieved the liver damage caused by high-fat diet, mainly manifested by the lowered levels of TC, TG, MDA, and IL-6 in the liver(P<0.01) and elevated levels of CAT and SOD in the liver. Furthermore, GPs reversed the intestinal flora disorder caused by high-fat diet, restored the diversity of intestinal flora, increased the relative abundance of Bacteroides, and reduced the relative abundance of Firmicutes and the ratio of Firmicutes to Bacteroides. Moreover, GPs promoted the proliferation of beneficial bacteria such as Akkermansia, Bacteroides, and Parabacteroides, and inhibited the growth of harmful bacteria such as Desulfovibrio, Escherichia-Shigella, and Helicobacter. GPs increased the content of short-chain fatty acids(acetic acid, propionic acid, and butyric acid)(P<0.01). These findings indicate that GPs can alleviate the high-fat diet-induced NAFLD in rats via regulating the intestinal flora and short-chain fatty acid metabolism.

Di'ao Xinxuekang alleviates non-alcoholic steatohepatitis in mice by up-regulating Nrf2/HO-1 signaling pathway / 中国中药杂志

The present study investigated the therapeutic effect and mechanism of Di'ao Xinxuekang(DXXK) on non-alcoholic steatohepatitis(NASH) in mice. Sixty-five C57 BL/6 J mice were randomly divided into a normal group and an experimental group for model induction with the high-fat diet for 16 weeks. Then the mice in the experimental group were randomly divided into a model group, an atorvastatin group(4 mg·kg~(-1)·d~(-1)), and high-(200 mg·kg~(-1)·d~(-1)), medium-(60 mg·kg~(-1)·d~(-1)), and low-dose(20 mg·kg~(-1)·d~(-1)) DXXK groups, with 10 mice in each group. Drugs were administered by gavage for eight weeks. Serum lipid, liver lipid, serum alanine aminotransferase(ALT), aspartate aminotransferase(AST), malondialdehyde(MDA), superoxide dismutase(SOD), and glutathione reductase(GSH-Px) were determined. Interleukin-1β(IL-1β) and tumor necrosis factor-α(TNF-α) were measured by enzyme-linked immunosorbent assay(ELISA). The liver index was calculated. The liver pathological change and lipid accumulation were observed by HE and oil red O staining. The liver ultrastructure was observed by the transmission electron microscope. The mRNA and protein expression of nuclear factor-erythroid 2 related factor 2(Nrf2) and heme oxygenase-1(HO-1) was detected by real-time fluorescence-based quantitative PCR and Western blot, respectively. The results showed that compared with the normal group, the model group displayed serum lipid and liver lipid metabolism disorders, elevated transaminase, lipid deposition, steatosis, and inflammation, suggesting that the NASH model in mice was properly induced. Compared with the model group, the DXXK groups showed decreased serum lipid, liver lipid, ALT, AST, MDA, IL-1β, and TNF-α, increased SOD and GSH-Px, alleviated hepatic steatosis, ballooning, and inflammation, and up-regulated Nrf2 and HO-1 gene and protein expression. In conclusion, DXXK can significantly alleviate NASH in mice, which is related to the inhibition of oxidative stress and inflammatory damage by up-regulating the Nrf2/HO-1 signaling pathway.

KLF9 regulates hepatic lipid metabolism via inducing CD36 expression / 生理学报

The development of nonalcoholic fatty liver disease (NAFLD) is closely related to the fatty acid (FA) uptake. This study aimed to investigate the effect of Krüppel-like factor 9 (KLF9) on CD36 (typical fatty acid translocase), hepatocellular lipid metabolism as well as the development and progression of nonalcoholic fatty liver. High-fat diet-induced obese C57BL/6J mice and db/db mice were used to test the expression levels of Klf9 and Cd36 in the livers. The primary hepatocytes were isolated from C57BL/6J mice, treated with Ad-GFP, Ad-Klf9, Ad-shCtrl or Ad-shKlf9, and then incubated with oleic acid and palmitic acid for 24 h. Liver-specific knockout of Klf9 mice were established. The protein levels and relative mRNA levels were examined by Western blot and real-time PCR, respectively. Triglyceride content was determined by using an assay kit. Lipid content was determined by Oil Red O staining. The results showed that: (1) Klf9 expression levels were increased in the livers of high-fat diet-induced obese mice and db/db mice, compared to their respective control mice. (2) Adenovirus-mediated overexpression of Klf9 in primary hepatocytes increased Cd36 expression and cellular triglyceride contents. (3) In contrast, adenovirus-mediated knockdown of Klf9 expression in primary hepatocytes by Ad-shKlf9 decreased Cd36 expression and cellular triglyceride contents. (4) Finally, Klf9 deficiency decreased liver Cd36 expression and alleviated fatty liver phenotype of high-fat diet-induced obese mice. These results suggest that KLF9 can regulate hepatic lipid metabolism and development of NAFLD by promoting the expression of CD36.

The role of SIRT6 in nonalcoholic steatohepatitis / 生理学报

SIRT6, a member of the silencing information regulatory protein family, is a nicotinamide adenine dinucleotide-dependent histone deacetylase and an ADP-ribose transferase enzyme. It plays an important role in fundamental physiological and pathological processes, including lipid metabolism, inflammation, oxidative stress and fibrosis, and is considered as a potential therapeutic target for metabolic syndrome. SIRT6 knockout mice displayed severe fatty liver, and the expression of SIRT6 in the liver of nonalcoholic steatohepatitis (NASH) mice was significantly lower than that of normal mice. Overexpression of SIRT6 significantly ameliorated NASH-induced liver damage. It is suggested that SIRT6 may play a key role in protecting against NASH. In this paper, we review the important regulatory functions of SIRT6 in the occurrence and development of NASH.

Estudo de parâmetros metabólicos em pacientes não diabéticos com doença hepática gordurosa não alcoólica - importância da dislipidemia / A study of metabolic parameters in non diabetic patients with non alcoholic fatty liver disease - importance of dyslipidemia

ABSTRACT BACKGROUND: Metabolic risk factors of non alcoholic fatty liver disease (NAFLD) in non diabetic teetotallers who constitute a definite group are not well defined. OBJECTIVE: To identify the metabolic risk factors of NAFLD if any in non diabetic subjects who do not consume alcohol. METHODS: In a cross sectional study the effect of metabolic parameters (BMI, individual lipid levels, hemoglobinA1c (HbA1c), HOMA IR and the metabolic syndrome components) of 150 consecutive non diabetic teetotallers (90 with normal glucose tolerance and 60 prediabetics) on their NFS (quantifiable severity parameter of NAFLD) was studied by linear regression analysis. Similar study was done in the normal glucose tolerance and prediabetes groups separately. These parameters were then compared with those of 75 matched diabetic teetotallers with NAFLD. To analyse further the difference between normal glucose tolerance, prediabetic and overt diabetic groups, binary logistic regression of the factors was carried out taking prediabetes and diabetes as outcome variable. RESULTS: All the metabolic parameters were significantly higher in diabetics compared to non diabetics and in prediabetics compared to those with normal glucose tolerance except high-density lipoprotein cholesterol. Triglyceride, high-density lipoprotein cholesterol and BMI significantly predicted NFS in the overall (adjusted R2 68.7%, P=0.000) and normal glucose tolerance groups (adjusted R2 73.2%, P=0.000) whereas BMI, triglyceride, low-density lipoprotein cholesterol and HbA1c did in prediabetics (adjusted R2 89%, P=0.000). The metabolic syndrome was significantly associated with NFS in the overall and prediabetic groups. High triglyceride (odds ratio1.08), low-density lipoprotein cholesterol (odds ratio1.03) and HbA1c (odds ratio 11.54) were positively associated with prediabetes compared to normal glucose tolerance group. CONCLUSION: In nondiabetic teetotallers dyslipidemias are the prime contributors to the development of NAFLD.

RESUMO CONTEXTO: Os fatores de risco metabólicos da doença hepática gordurosa não alcoólica (DHGNA) em abstêmios não diabéticos, que constituem um grupo distinto, não são bem definidos. OBJETIVO: Identificar os fatores de risco metabólicos da DHGNA em indivíduos não diabéticos e que não consumam álcool. MÉTODOS: Em um estudo transversal, o efeito dos parâmetros metabólicos (IMC, níveis de lipídios individuais, HbA1c, Homa IR e os componentes da síndrome metabólica) de 150 abstêmios não diabéticos consecutivos (90 com tolerância à glicose normal e 60 pré-diabéticos) em sua NFS (parâmetro de gravidade quantificável da DHGNA) foram estudados por análise de regressão linear. Um estudo similar em separado foi feito nos grupos normais da tolerância da glicose e do pré-diabetes. Esses parâmetros foram comparados com os de 75 abstêmios diabéticos pareados com DHGNA. Para analisar ainda mais a diferença entre a tolerância à glicose normal foi realizada a regressão logística binária dos fatores tomando pré-diabetes e diabetes como variável de desfecho, nos grupos diabéticos e pré-diabéticos. RESULTADOS: Todos os parâmetros metabólicos foram significativamente maiores nos diabéticos comparados aos não diabéticos e em pré-diabéticos comparados àqueles com tolerância normal à glicose, exceto HDL. Os índices TG, HDL e IMC previram significativamente o NFS no geral nos grupos de tolerância normal (R2 ajustado 68,7%, P=0,000) e de glicose normal (R2 ajustado 73,2%, P=0,000), enquanto o IMC, TG, LDL e HbA1c predisseram em pré-diabéticos (R2 ajustado 89%, P=0,000). A síndrome metabólica foi associada significativamente com o NFS nos grupos totais e pré-diabéticos. O TG elevado (odds ratio 1,08), o LDL (odds ratio 1,03) e a HbA1c (odds ratio 11,54) foram positivamente associados ao pré-diabetes em comparação com o grupo normal de tolerância à glicose. CONCLUSÃO: Em abstêmios não diabéticos as dislipidemias são os principais contribuintes para o desenvolvimento da DHGNA.

Tendências temporais da prevalência de Helicobacter pylori em Itajaí - SC: um estudo retrospectivo de 25 anos baseado em banco de dados endoscópicos / Time trends of helicobacter pylori prevalence in itajaí - sc: a retrospective study of 25 years based on endoscopic database

ABSTRACT BACKGROUND: The bacterium Helicobacter pylori is strongly associated with the development of gastric adenocarcinoma. Currently, the prevalence in developed countries is 40%, but this value increases considerably in developing countries, which can reach rates bigger than 90%. OBJECTIVE: The objective of this study was to determine the mean and annual prevalence of Helicobacter pylori infection in patients from Itajaí during the period from July 1992 to April 2016, as well as the gender and age groups most affected. METHODS: After consent of the clinical director of the Gastroclinica Itajaí and confidentiality commitment about the research, the database of the Endoscopy Service of the clinic was evaluated. All the patients who underwent their first upper digestive endoscopy with urease test and/or histological analysis were included. The data were submitted to statistical analysis of prevalence by gender, age group and years of study, with subsequent correction through the confidence interval. RESULTS: The mean prevalence of Helicobacter pylori infection thru all years of study was 50.07%. With the calculation of the annual prevalences, it was evident the gradual reduction of infection in the population of Itajaí, that was 81.3% in 1992, declining to 33% in the year of 2016. When classifying the prevalence of infection by gender, it was higher in males (53.59%), and gender distribution by age group showed no statistically significant difference among genders between the ages of 40 and 80 years. In relation to the age group, the highest prevalence was in the group between 40 and 49 years. CONCLUSION: Although this study is retrospective and based on endoscopic database analysis, without access to clinical data of patients such as prior use of proton pump inhibitor and antibiotics to endoscopy, its results are important because they may reflect the current panorama of Helicobacter pylori infection in the city under study, where it has been presenting a gradual reduction of prevalence over the years, with current rates similar to that of developed countries (33%). Future studies are needed to confirm our data.

RESUMO CONTEXTO: A bactéria Helicobacter pylori associa-se fortemente ao desenvolvimento do adenocarcinoma gástrico. Atualmente, a prevalência em países desenvolvidos é de 40%, porém esse valor cresce consideravelmente em países em desenvolvimento, que chegam a alcançar taxas de até 90%. OBJETIVO: O objetivo desta pesquisa foi determinar a prevalência média e anual da infecção por Helicobacter pylori nos pacientes de Itajaí durante o período de julho de 1992 a abril de 2016, assim como o sexo e as faixas etárias mais acometidas. MÉTODOS: Após consentimento do diretor técnico da Gastroclínica Itajaí e comprometimento de sigilo em relação à pesquisa, foi avaliada a base de dados do Serviço de Endoscopia da clínica. Foram selecionados todos os pacientes que realizaram pela primeira vez o exame de endoscopia digestiva alta com teste da urease e/ou análise histológica. Os dados obtidos foram submetidos à análise estatística de prevalência por sexo, faixa etária e anos do estudo, com posterior correção dos dados através do intervalo de confiança. RESULTADOS: A prevalência média da infecção por Helicobacter pylori em todos os anos de estudo foi de 50,07%. Com o cálculo das prevalências anuais, ficou evidente a redução gradual da infecção na população de Itajaí, que era de 81,3% em 1992, passando a 33% no ano de 2016. Ao classificar a prevalência da infecção por gênero, foi maior no sexo masculino (53,59%) e a distribuição dos gêneros por faixa etária não mostrou diferença estatisticamente significativa entre os sexos entre as idades de 40 a 80 anos. Em relação à faixa etária, a maior prevalência foi no grupo entre 40 e 49 anos. CONCLUSÃO: Embora este estudo seja retrospectivo e baseado em análise de banco de dados de endoscopias digestivas, sem acesso a dados clínicos de pacientes como uso prévio de nibidor de bomba de próton e antibióticos à endoscopia, seus resultados são importantes, pois podem refletir o panorama atual da infecção por Helicobacter pylori no município em estudo, que vem apresentando uma redução gradual da prevalência ao longo dos anos, com taxas atuais semelhantes às dos países desenvolvidos (33%). Estudos futuros são necessários para confirmar nossos dados.

Correlação entre a circunferência do pescoço e resistência a insulina em pacientes com DHGNA / The correlation of neck circumference and insulin resistance in nafld patients

ABSTRACT BACKGROUND: Insulin resistance, especially that induced by obesity, plays a central role in the development of non-alcoholic fatty liver disease. Although the evaluation of overweight patients is important, the nutritional assessment tools used in clinical practice have limitations. Neck circumference (NC), from this, becomes a viable and low-cost alternative, which seems to be related to the accumulation of fat in the hepatic tissue. OBJECTIVE: To evaluate the association between NC and metabolic alterations in patients with non- alcoholic fatty liver disease. METHODS: A cross-sectional study performed in 82 patients, of whom 76 underwent liver biopsy. We performed weight, height, abdominal circumference and NC measures. Values of NC ≥42 cm and ≥36 cm were considered as altered for men and women, respectively. Laboratory tests and liver biopsy result were collected in the participants' charts. We evaluated fasting blood glucose levels, insulin, glycosylated hemoglobin, triglycerides, total cholesterol, high density lipoprotein (HDL-C), low density lipoprotein (LDL-C), ferritin, alkaline phosphatase, gamma glutamyltransferase, albumin, total bilirubin, direct bilirubin, glutamic-oxalacetic transaminase, glutamic-pyruvic transaminase and the HOMA-IR index. RESULTS: We evaluated eighty-two patients. Patients with altered NC had increased body mass index (P=0.043), abdominal circumference (P=0.007), insulin (P=0.003) and HOMA-IR (P=0.029) when compared to those with adequate NC. NC was significantly correlated with reduced levels of high-density cholesterol (HDL-C) in men (r= -042, P<0.05), increased insulin levels in men and female (rs=0.47; P<0.05 and rs=0.51; P<0.01, respectively), as well as higher HOMA-IR index both males (rs=0.49; P<0.01) and female (rs=0.30; P<0.05). There was no significant association between NC and liver outcomes (r=0.145; P=0.36). CONCLUSION: NC is associated with the HOMA-IR index in patients with non-alcoholic fatty liver disease. NC can be used in the screening of insulin resistance in these patients, considering that insulin resistance plays a key role in the progression of the disease.

RESUMO CONTEXTO: A resistência à insulina, em especial a induzida pela obesidade, desempenha papel central no desenvolvimento da doença hepática gordurosa não alcoólica (DHGNA). Embora seja importante a avaliação de pacientes com excesso de peso, as ferramentas de avaliação nutricional utilizadas na prática clínica apresentam limitações. A circunferência do pescoço, a partir disso, torna-se uma alternativa viável e de baixo custo, a qual parece estar relacionada ao acúmulo de gordura no tecido hepático. OBJETIVO: Avaliar a associação entre a circunferência do pescoço (CP) e as alterações metabólicas em pacientes com DHGNA. MÉTODOS: Estudo transversal realizado em 82 pacientes, dos quais 76 foram submetidos à biópsia hepática. Foram realizadas as medidas de peso, altura, circunferência abdominal e CP. Valores de CP ≥42 cm e ≥36 cm foram considerados alterados para homens e mulheres, respectivamente. Os exames laboratoriais e o resultado da biópsia hepática foram coletados dos prontuários dos participantes. Foram avaliados os níveis glicêmicos em jejum, insulina, hemoglobina glicosilada, triglicerídeos, colesterol total, lipoproteína de alta densidade (HDL-C), lipoproteína de baixa densidade (LDL-C), ferritina, fosfatase alcalina, gama glutamiltransferase, albumina, bilirrubina total, bilirrubina direta, transaminase glutâmico-oxalacética, transaminase glutâmico-pirúvica e o índice HOMA-IR. RESULTADOS: Foram avaliados 82 pacientes. Os pacientes com CP alterada apresentaram aumento do índice de massa corporal (P=0,043), circunferência abdominal (P=0,007), insulina (P=0,003) e HOMA-IR (P=0,029) quando comparados àqueles com CP adequada. A CP foi significativamente correlacionada com níveis reduzidos de colesterol de alta densidade (HDL-C) em homens (r= -042, P<0,05), aumento dos níveis de insulina em homens e mulheres (rs=0,47, P<0,05 e rs = 0,51; P<0,01, respectivamente), bem como maior índice HOMA-IR, tanto do sexo masculino (rs=0,49; P<0,01) quanto do feminino (rs=0,30; P<0,05). Não houve associação significativa entre CP e os desfechos hepáticos (r=0,145, P=0,36). CONCLUSÃO: A CP está associada com o índice HOMA-IR em pacientes com DHGNA. A CP pode ser utilizada no rastreamento da resistência à insulina nesses pacientes, considerando que a resistência à insulina desempenha um papel fundamental na progressão da doença.

Oxidative stress on ischemia/reperfusion injury in mice with non-alcoholic hepatic steatosis or steatohepatitis

Abstract Purpose: To evaluate the oxidative stress, resulting from ischemia and hepatic reperfusion, in mice with non-alcoholic hepatic steatosis and steatohepatitis. Methods: C57BL/6 male mice were used. Part of them were ob/ob mice, and the other part was fed with standard or MCD diets - this last used to develop steatohepatitis. The animals - MCD-I/R, ob/ob-I/R and I/R groups - were submitted to 30 minutes of partial hepatic ischemia, followed by reperfusion for 24 hours. The blood was collected, for biochemical analysis of AST, and the liver removed for assessment of TBARS and nitrite, and of histology. Results: After the I/R, the animal fed with MCD diet presented higher AST levels (MCD-I/R: 967±349U/L / ob/ob-I/R: 606±18 U/L / I/R: 311±172 U/L), TBARS (MCD-I/R: 7±1 nM/mg protein / ob/ob-I/R: 3±1 nM/mg protein / I/R: 3±1 nM/mg protein) and nitrite (MCD-I/R: 614±87 µg/mL / ob/ob-I/R: 512±81 µg/mL / I/R: 459±29 µg/mL) than the ob/ob mice, when both groups were compared to animals fed with standard diet. Regarding histology, the steatosis level (azonal macrovesicular steatosis of level 3 - >66%) and hepatic fibrosis (periportal and perisinusoidal of level 2) was also more intense, but both animal models presented lobular inflammation of level 3 (>66%). Conclusions: The murine model fed with MCD diet is suitable for the assessment of oxidative stress in hepatic I/R injury associated with the nonalcoholic fatty liver disease. Although both murine models showed inflammatory infiltrate and macro and micro vesicular steatosis.

Effect of curcumin on visfatin and zinc-α2-glycoprotein in a rat model of non-alcoholic fatty liver disease

ABSTRACT PURPOSE: To investigate the effect of curcumin on visfatin and zinc-α2-glycoprotein (ZAG) expression levels in rats with non-alcoholic fatty liver disease (NAFLD). METHODS: Fifty-six male rats were randomly divided into a control group (n=16) and model group (n=40) and were fed on a normal diet or a high-fat diet, respectively. Equal volumes of sodium carboxymethyl cellulose (CMC) were intragastrically administered to the control group for 4 weeks. At the end of the 12th week, visfatin and ZAG protein expression levels were examined by immunohistochemistry. Visfatin mRNA levels were measured by semi-quantitative reverse transcription polymerase chain reaction. RESULTS: Compared with the control group, the model group showed significantly increased expression of visfatin in liver tissue (P < 0.01) and significantly decreased expression of ZAG (P < 0.01). These effects were ameliorated by curcumin treatment. CONCLUSIONS: Visfatin and zinc-α2-glycoprotein may be involved in the pathogenesis of NAFLD. Treatment of NAFLD in rats by curcumin may be mediated by the decrease of visfatin and the increase of non-alcoholic fatty liver disease.

Non-alcoholic steatohepatitis-related liver cirrhosis is increasing in China: A ten-year retrospective study

OBJECTIVE: Little is known about metabolic factors in cirrhotic patients in China. Therefore, we aimed to quantify the prevalence of both metabolic factors and non-alcoholic steatohepatitis-related liver cirrhosis in China. METHODS: The medical records of 1,582 patients diagnosed with liver cirrhosis from June 2003 to July 2013 at Daping Hospital (Chongqing, China) were retrospectively reviewed through a computer-generated search. RESULTS: Serum hepatitis B virus surface antigen was present in 1,083 (68.5%) patients, and hepatitis B was found to be the only etiological factor in 938 (59.3%) of all patients. Obesity, diabetes mellitus, and arterial hypertension were observed in 229 (14.5%), 159 (10.1%), and 129 (8.2%) patients, respectively. From 2012-2013, the proportion of non-alcoholic steatohepatitis-related liver cirrhosis increased to 3.2%, whereas the average proportion of non-alcoholic steatohepatitis-related liver cirrhosis in the previous ten years was 1.9%. The incidence of hepatocellular carcinoma was much higher in males than in females (6.3% vs. 3.7%, respectively, p=0.036). Obesity and diabetes mellitus did not significantly increase the incidence of hepatocellular carcinoma in the whole cirrhotic group. The presence of hepatitis B virus was the only risk factor for hepatocellular carcinoma in cirrhotic patients (p<0.001). CONCLUSIONS: Although hepatitis B virus remains the main etiology of liver cirrhosis in China, steatohepatitis-related liver cirrhosis is increasing in frequency. Hepatitis B virus was the sole significant risk factor for hepatocellular carcinoma in the whole cirrhotic group in the present study, in contrast to obesity and diabetes mellitus, for which only a trend of increased hepatocellular carcinoma was found. .

Effect of physical training on liver expression of activin A and follistatin in a nonalcoholic fatty liver disease model in rats

Nonalcoholic fatty liver disease (NAFLD) is characterized by fat accumulation in the liver and is associated with obesity and insulin resistance. Activin A is a member of the transforming growth factor beta (TGF)-β superfamily and inhibits hepatocyte growth. Follistatin antagonizes the biological actions of activin. Exercise is an important therapeutic strategy to reduce the metabolic effects of obesity. We evaluated the pattern of activin A and follistatin liver expression in obese rats subjected to swimming exercise. Control rats (C) and high-fat (HF) diet-fed rats were randomly assigned to a swimming training group (C-Swim and HF-Swim) or a sedentary group (C-Sed and HF-Sed). Activin βA subunit mRNA expression was significantly higher in HF-Swim than in HF-Sed rats. Follistatin mRNA expression was significantly lower in C-Swim and HF-Swim than in either C-Sed or HF-Sed animals. There was no evidence of steatosis or inflammation in C rats. In contrast, in HF animals the severity of steatosis ranged from grade 1 to grade 3. The extent of liver parenchyma damage was less in HF-Swim animals, with the severity of steatosis ranging from grade 0 to grade 1. These data showed that exercise may reduce the deleterious effects of a high-fat diet on the liver, suggesting that the local expression of activin-follistatin may be involved.

Duodenal jejunal bypass attenuates non-alcoholic fatty liver disease in western diet-obese rats

PURPOSE: To evaluate the effects of duodenal-jejunal bypass (DJB) on serum and hepatic profiles of obese rats fed on a western diet (WD). METHODS: Twenty eight male Wistar rats were fed a standard rodent chow diet (CTL group) or WD ad libitum. After 10 weeks, WD rats were submitted to sham (WD SHAM) or duodenal-jejunal bypass (WD DJB). Body weight, fat pad depots, glycemia, insulinemia, HOMA-IR, TyG, lipids profile and hepatic analyses were evaluated two months after surgery. RESULTS: The WD SHAM group presented greater obesity, hyperglycemia, hyperinsulinemia, insulin resistance, hypertriglyceridemia and hepatic steatosis than the CTL group. WD DJB rats presented decreased serum glucose and insulin resistance, when compared to WD SHAM animals, without changes in insulinemia. In addition, DJB surgery normalized serum TG and attenuated TG accumulation and steatosis in the liver of the WD DJB group. Hepatic ACC and FAS protein expressions were similar in all groups. CONCLUSION: Duodenal-jejunal bypass attenuates hepatic parameters of non-alcoholic fatty liver disease in obese rats fed on a western diet. .