RESUMEN
Bardet-Biedl syndrome (BBS) is a rare autosomal recessive ciliopathy, which is caused by mutations mainly in genes encoding BBSome complex and IFT complex. Here, we reported a 21-year-old female with BBS characterized by three primary features including obesity, retinitis pigmentosa sine pigmento and bilateral renal cysts. She also had some secondary features such as diabetes mellitus, nonalcoholic fatty liver disease, subclinical hypothyroidism and mild conductive hearing damage. Whole exome sequencing revealed two compound heterozygous mutations in exon 2 of the BBS12 gene (c.188delC, p.T63fs and c.1993_1995del, p.665_665del) in this patient. Sanger sequencing showed that her father and mother carried c.188delC (p.T63fs) and c.1993_1995del (p.665_665del) variants, respectively, while her parents were free of BBS-related symptoms. In conclusion, this case reported two novel mutations (c.188delC, p.T63fs and c.1993_1995del, p.665_665del) of the BBS12 gene in a girl presented with BBS, which provides novel genetic resources for studies of the disease. Meanwhile, the BBS case shows the entire development progress from her birth to adulthood, which helps facilitate clinicians' understanding of BBS.
Asunto(s)
Síndrome de Bardet-Biedl , Humanos , Femenino , Adulto , Adulto Joven , Síndrome de Bardet-Biedl/genética , Síndrome de Bardet-Biedl/diagnóstico , Pruebas Genéticas , Mutación , ExonesRESUMEN
Hepatic steatosis is a hallmark of nonalcoholic fatty liver disease (NAFLD) and is promoted by dysregulated de novo lipogenesis. ATP-citrate lyase (ACLY) is a crucial lipogenic enzyme that is up-regulated in individuals with NAFLD. A previous study has shown that acetylation of ACLY at Lys-540, Lys-546, and Lys-554 (ACLY-3K) increases ACLY protein stability by antagonizing its ubiquitylation, thereby promoting lipid synthesis and cell proliferation in lung cancer cells. But the functional importance of this regulatory mechanism in other cellular or tissue contexts or under other pathophysiological conditions awaits further investigation. Here, we show that ACLY-3K acetylation also promotes ACLY protein stability in AML12 cells, a mouse hepatocyte cell line, and found that the deacetylase sirtuin 2 (SIRT2) deacetylates ACLY-3K and destabilizes ACLY in these cells. Of note, the livers of mice and humans with NAFLD had increased ACLY protein and ACLY-3K acetylation levels and decreased SIRT2 protein levels. Mimicking ACLY-3K acetylation by replacing the three lysines with three glutamines (ACLY-3KQ variant) promoted lipid accumulation both in high glucose-treated AML12 cells and in the livers of high-fat/high-sucrose (HF/HS) diet-fed mice. Moreover, overexpressing SIRT2 in AML12 cells inhibited lipid accumulation, which was more efficiently reversed by overexpressing the ACLY-3KQ variant than by overexpressing WT ACLY. Additionally, hepatic SIRT2 overexpression decreased ACLY-3K acetylation and its protein level and alleviated hepatic steatosis in HF/HS diet-fed mice. Our findings reveal a posttranscriptional mechanism underlying the up-regulation of hepatic ACLY in NAFLD and suggest that the SIRT2/ACLY axis is involved in NAFLD progression.
Asunto(s)
ATP Citrato (pro-S)-Liasa/metabolismo , Enfermedad del Hígado Graso no Alcohólico/patología , ATP Citrato (pro-S)-Liasa/antagonistas & inhibidores , ATP Citrato (pro-S)-Liasa/genética , Acetilación , Animales , Línea Celular , Dieta Alta en Grasa , Glucosa/farmacología , Humanos , Metabolismo de los Lípidos/efectos de los fármacos , Hígado/metabolismo , Hígado/patología , Masculino , Ratones , Ratones Endogámicos C57BL , Mutagénesis Sitio-Dirigida , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Estabilidad Proteica , Interferencia de ARN , ARN Interferente Pequeño/metabolismo , Sirtuina 2/genética , Sirtuina 2/metabolismoRESUMEN
BACKGROUND: Recent studies have linked non-alcoholic fatty liver disease (NAFLD) to a reduced bone mineral density (BMD). We aimed to detect the quantitative association of liver fat content (LFC) and serum alanine aminotransferase (ALT) with BMD in a middle-aged and elderly Chinese population. METHODS: The lumbar spine, hip and whole body BMDs were measured using dual-energy x-ray absorptiometry (Lunar iDXA, GE Healthcare) in 1659 Chinese (755 men and 1028 postmenopausal women) from Shanghai Changfeng community. Liver fat content was quantified via an ultrasound quantitative method. Multivariate linear regression analyses were carried out to determine the independent association of LFC and serum ALT with BMD and bone metabolic biomarkers. We also attempted to investigate the synergistic association between LFC and ALT as risk factors for bone mineral loss in Chinese. RESULTS: Subjects with higher LFC had significantly lower BMD at all skeletal sites. Univariate correlation analysis showed that both LFC and ALT were inversely associated with BMD at the spine (r = -0.116, P < 0.001 and r = -0.102, P = 0.005), hip (r = -0.095, P = 0.014 and r = -0.075, P = 0.041) and whole body sites (r = -0.134, P < 0.001 and r = -0.164, P < 0.001) in men. After confounders were controlled for, LFC and ALT remained associated with BMD and bone formation biomarkers in men, but not postmenopausal women. When both NAFLD and elevation of ALT were present, there was a significant synergistic worsening of the BMDs at all bone sites. CONCLUSIONS: Liver fat content and serum ALT were inversely correlated with BMD in middle-aged and elderly men. The underlying mechanism might relate to a reduction in osteoblast activity. Elevation of the hepatotoxic biomarker ALT may indicate high risk for osteoporosis in patients with NAFLD.
Asunto(s)
Adiposidad , Alanina Transaminasa/sangre , Pueblo Asiatico , Densidad Ósea , Hígado/metabolismo , Posmenopausia/sangre , Anciano , Anciano de 80 o más Años , Biomarcadores/sangre , China , Demografía , Femenino , Humanos , Modelos Lineales , Masculino , Persona de Mediana Edad , Factores de RiesgoRESUMEN
OBJECTIVE: To explore the liver disease spectrum in patients with type 2 diabetes (T2DM) and the risk factors of non-alcoholic fatty liver disease (NAFLD). METHODS: From September 2009 to October 2011, 1069 hospitalized patients with T2DM in Department of Endocrinology and Metabolism were involved in the study. The history informations, results of laboratory examination, hepatic ultrasound and hepatic proton magnetic resonance spectrum ((1)H MRS) of all patients were collected to analysis. RESULTS: (1) The detectable rate of raised liver enzymes in T2DM patients was 28.7% (307/1069), composed mainly of NAFLD (39.4%, 121/307). After excluding the factors such as alcoholic abuse, viral hepatitis, the detect rate of raised liver enzymes in T2DM patients was 26.9% (185/688). (2) The detectable rate of fatty liver by ultrasound in T2DM patients was 56.7% (500/882), composed mainly of NAFLD (72.6%, 363/500), and the detectable rate of NAFLD was 58.0% (363/626). (3) The detectable rate of fatty liver by hepatic (1)H MRS was 72.8% (227/312), composed mainly of NAFLD (69.6%, 158/227). The detectable rate of NAFLD was 69.6% (158/227). (4) Of the three methods for diagnosing NAFLD, (1)H MRS had the highest detectable rate, followed by ultrasound, and the hepatic enzymes was the lowest. Set the hepatic (1)H MRS as gold diagnosing standard of NAFLD, the combination of hepatic enzymes and ultrasound increase the sensitivity. The optional cut-off points of ALT were 19.7 U/L (male, ROCAUC = 0.689, P < 0.01) and 17.0 U/L (female, ROCAUC = 0.727, P < 0.01). (5) Logistic stepwise regression analysis showed sex, BMI, hemoglobin, fasting C-peptide and uric acid (OR = 3.803, 1.195, 1.037, 2.896, 1.011, all P < 0.05) were positively correlated with NAFLD, and diabetes duration (OR = 0.948, P < 0.05) was positively correlated with NAFLD independently. CONCLUSIONS: The detectable rate of fatty liver was high in T2DM which was composed mainly of NAFLD. High abnormal liver enzymes detectable rate indicated that NAFLD with T2DM are prone to NASH.
Asunto(s)
Diabetes Mellitus Tipo 2 , Hígado Graso/epidemiología , Hepatopatías/epidemiología , Adulto , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/enzimología , Femenino , Humanos , Pacientes Internos , Hígado/enzimología , Masculino , Persona de Mediana Edad , Enfermedad del Hígado Graso no Alcohólico , Estudios Retrospectivos , Factores de RiesgoRESUMEN
The effect of uric acid (UA) on the pathogenesis of metabolic disorders is highly dependent on its physicochemical properties, and hyperuricaemia associated with different conditions may have different clinical meanings. The aim of the present study was to investigate the association of serum UA levels with metabolic syndrome and non-alcoholic fatty liver disease (NAFLD) in a middle-aged and elderly population with normal and impaired renal function. The cross-sectional study was performed on 1141 participants (426 men, 715 women; mean age 62 years) enrolled from the Shanghai Changfeng community. Each participant underwent a standard interview, with anthropometric and laboratory measurements. Hepatic fat content (HFC) was determined by a newly established quantitative ultrasound method. Univariate correlation analysis showed that serum UA was associated with all components of metabolic syndrome and HFC (r = 0.193, P < 0.001), especially in participants with a normal estimated glomerular filtration rate (eGFR; r = 0.255, P < 0.001). Logistic regression analysis demonstrated an independent association of serum UA with metabolic syndrome and NAFLD in participants with normal renal function, but not in those with eGFR < 90 mL/min per 1.73 m(2) . Furthermore, multivariate linear analysis showed that UA levels were independently associated with HFC (P = 0.003), but only in participants with normal eGFR. Elevated serum UA is independently associated with metabolic syndrome and NAFLD in patients with normal renal excretory function. However, in those with renal insufficiency, hyperuricaemia has no association with metabolic disorders.
Asunto(s)
Riñón/fisiopatología , Hígado/metabolismo , Síndrome Metabólico/sangre , Síndrome Metabólico/fisiopatología , Ácido Úrico/sangre , Anciano , Pueblo Asiatico , Estudios de Cohortes , Estudios Transversales , Hígado Graso/sangre , Hígado Graso/metabolismo , Hígado Graso/fisiopatología , Femenino , Tasa de Filtración Glomerular/fisiología , Humanos , Hiperuricemia/sangre , Hiperuricemia/metabolismo , Hiperuricemia/fisiopatología , Masculino , Síndrome Metabólico/metabolismo , Persona de Mediana Edad , Enfermedad del Hígado Graso no Alcohólico , Estudios ProspectivosRESUMEN
BACKGROUND: The study was undertaken to examine the effects of berberine (BBR) on serum homocysteine, lipids and the aortic lesion in Sprague-Dawley (SD) rats fed with a long-term high-fat diet (HFD). METHODS: Healthy male SD rats weighing 190-210 g received randomly standard diet or a high-fat diet for 24 weeks. After 8 weeks of feeding, rats fed with HFD were randomized to receive berberine (200 mg · kg-1· day-1) or vehicle by gavage for 16 weeks. After overnight fasting, all rats were sacrificed and total blood samples were also collected for determinant of fasting serum homocysteine (Hcy), total cholesterol (TC) and low density lipoprotein cholesterol (LDL-c) levels. The aorta was stained with hematoxylin and eosin (HE) and Sudan Ш to evaluate aortic lesion. The livers were dissected out and snap-frozen in liquid nitrogen for hepatic TC content and molecular analysis. 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMGR), Lipoprotein receptors and apolipoproteins gene expression in the liver were determined by real-time PCR. RESULTS: Intragastrical administration with berberine for 16 weeks lowered serum Hcy in rats fed with a high-fat diet. In parallel, it also decreased body weight and improved serum TC and LDL-c. Berberine also tended to decrease hepatic cholesterol. Consistently, berberine also upregulated LDL receptor (LDLR) mRNA level and suppressed HMGR gene expression. Meanwhile, upon berberine-treated rats, there was a significant increase in apolipoprotein E (apoE) mRNA, but no change in apoAI and scavenger receptor (SR) mRNA in the liver. Further, no atherosclerotic lesions were developed in berberine-treated rats for 16 weeks. CONCLUSION: Berberine can counteract HFD-elicited hyperhomocysteinemia and hyperlipidemia partially via upregulating LDLR and apoE mRNA levels and suppressing HMGR gene expression.
Asunto(s)
Berberina/farmacología , Hiperhomocisteinemia/tratamiento farmacológico , Hiperlipidemias/tratamiento farmacológico , Hipolipemiantes/farmacología , Animales , Aorta/efectos de los fármacos , Aorta/patología , Apolipoproteínas/genética , Apolipoproteínas/metabolismo , Aterosclerosis/prevención & control , Berberina/uso terapéutico , Colesterol/metabolismo , LDL-Colesterol/sangre , Dieta Alta en Grasa/efectos adversos , Evaluación Preclínica de Medicamentos , Homocisteína/sangre , Hidroximetilglutaril-CoA Reductasas/genética , Hidroximetilglutaril-CoA Reductasas/metabolismo , Hiperhomocisteinemia/sangre , Hiperhomocisteinemia/etiología , Hiperlipidemias/sangre , Hiperlipidemias/etiología , Hipolipemiantes/uso terapéutico , Lípidos/sangre , Hígado/metabolismo , Masculino , Ratas , Ratas Sprague-Dawley , Receptores de Lipoproteína/genética , Receptores de Lipoproteína/metabolismo , Factores de RiesgoRESUMEN
BACKGROUND: Bariatric surgery has emerged as the most effective therapy for morbid obesity. There is increasing evidence that bariatric surgery could alleviate systemic inflammation and influence thyroid function. The current study aimed to investigate the associations of preoperative thyroid autoimmune status with the changes in body weight and thyroid function after bariatric surgery. METHODS: We recruited 101 patients with morbid obesity (44 men and 57 women) who received bariatric surgery at Zhongshan Hospital, Fudan University. Those who had used thyroid hormone replacement or antithyroid drugs were excluded. General linear models were used to compare the changes in body weight and thyroid function in participants with different thyroid autoimmune statuses. RESULTS: After bariatric surgery, serum-free triiodothyronine (FT3) (4.94 ± 0.73 vs 4.33 ± 0.59 pmol/L, P < 0.001) and thyroid-stimulating hormone (TSH) (3.13 ± 1.59 vs 2.26 ± 1.26 µIU/mL, P < 0.001) were significantly reduced, accompanied by reductions in BMI (42.1 ± 7.6 vs 31.4 ± 6.5 kg/m2, P < 0.001), and estimated basal metabolic rate (2002 ± 398 vs 1700 ± 336 kcal/day, P = 0.001) and an improvement in lipid profiles. Serum thyroperoxidase antibody (TPOAb) and thyroglobulin antibody (TgAb) levels also decreased significantly from 79.3 and 177.1 IU/mL to 57.8 and 66.0 IU/mL in participants with positive thyroid antibodies (P < 0.05). Further analysis showed that the positive preoperative thyroid autoimmune status was associated with less reduction in serum TSH (0.05 ± 1.59 vs - 1.00 ± 1.43 µIU/mL, P = 0.021) and BMI (- 8.3 ± 3.6 vs - 11.0 ± 4.5 kg, P = 0.049) after bariatric surgery. CONCLUSION: Our study highlights a group of patients with morbid obesity, who have positive preoperative thyroid autoimmunity and less reduction in serum TSH levels and body weight after bariatric surgery.
Asunto(s)
Cirugía Bariátrica , Obesidad Mórbida/sangre , Obesidad Mórbida/cirugía , Glándula Tiroides/fisiopatología , Tirotropina/sangre , Adulto , Autoanticuerpos , Autoantígenos , Autoinmunidad , Femenino , Humanos , Yoduro Peroxidasa , Proteínas de Unión a Hierro , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Pruebas de Función de la TiroidesRESUMEN
BACKGROUND & AIMS: Non-alcoholic fatty liver disease (NAFLD) is a common and strong risk factor for cardiovascular disease and hepatocellular carcinoma. The rapid acceleration of the increase in NAFLD prevalence has exceeded the trends observed for obesity, and has been driven by multiple factors. The aim of this study was to investigate the correlation between the serum levels of folic acid, the endogenous source of methyl groups for DNA methylation, and NAFLD in Chinese adults. METHODS: The correlations between the serum folic acid levels and NAFLD were investigated in two independent cohorts of 70 subjects who underwent a liver biopsy and 130 subjects with varying liver fat contents, as measured using proton magnetic resonance spectroscopy (1H-MRS). Independent correlations between serum folic acid levels and liver steatosis grades were detected using a multivariate ordinal regression analysis. The diagnostic performances of serum folic acid levels alone and in combination with existing NAFLD prediction scores were compared with those of traditional NAFLD prediction parameters using receiver operating characteristic (ROC) curve analyses. RESULTS: Serum folic acid concentrations were inversely correlated with liver histological steatosis grades (ρ = -0.371, P < 0.001) and the 1H-MRS-measured liver fat content (r = -0.199, P = 0.038). According to the multivariate ordinal regression analysis, serum folic acid levels were inversely correlated with liver steatosis grades (OR 0.739 [0.594-0.918], P = 0.006) independent of age, gender, BMI, components of metabolic syndrome and the serum TC, LDL-c and HOMA-IR levels. The AUROC of serum folic acid for the diagnosis of NAFLD was 0.75 (0.65-0.83), and the addition of serum folic acid to NAFLD prediction scores significantly improved the diagnostic prediction of NAFLD (AUROC = 0.88 [0.81-0.94]). CONCLUSION: Low serum folic acid levels were identified as an independent risk factor for NAFLD in the Chinese population. The addition of the serum folic acid levels to the current existing NAFLD prediction scores significantly improved the prediction of NAFLD.
Asunto(s)
Ácido Fólico/sangre , Enfermedad del Hígado Graso no Alcohólico/sangre , Adulto , Anciano , Pueblo Asiatico , Biopsia , China , Metilación de ADN , Femenino , Humanos , Hígado/patología , Masculino , Persona de Mediana Edad , Enfermedad del Hígado Graso no Alcohólico/patología , Espectroscopía de Protones por Resonancia Magnética , Curva ROCRESUMEN
OBJECTIVES: Presence of non-alcoholic fatty liver disease (NAFLD) can predict risks for diabetes, cardiovascular disease and advanced liver disease in the general population. We aimed to establish a non-invasive score for prediction of NAFLD in Han Chinese, the largest ethnic group in the world, and detect whether ethnicity influences the accuracy of such a score. METHODS: Liver fat content (LFAT) was measured by quantitative ultrasound in 3548 subjects in the Shanghai Changfeng Community and a Chinese score was created using multivariate logistic regression analyses. This new score was internally validated in Chinese and externally in Finns. Its diagnostic performance was compared to the NAFLD liver fat score, fatty liver index (FLI) and hepatic steatosis index (HSI) developed in Finns, Italians and Koreans. We also analyzed how obesity related to LFAT measured by 1H-MRS in 79 Finns and 118 Chinese with type 2 diabetes (T2D). RESULTS: The metabolic syndrome and T2D, fasting serum insulin, body mass index (BMI) and AST/ALT ratio were independent predictors of NAFLD in Chinese. The AUROC in the Chinese validation cohort was 0.76 (0.73-0.78) and in Finns 0.73 (0.68-0.78) (p<0.0001). 43%, 27%, 32% and 42% of Chinese had NAFLD when determined by the Chinese score, NAFLD liver fat score (p<0.001 vs. Chinese score), FLI (p<0.001) and HSI (NS). For any given BMI and waist circumference, the Chinese had a markedly higher LFAT than the Finns. CONCLUSION: The predictors of NAFLD in Han Chinese are as in Europids but the Chinese have more LFAT for any given degree of obesity than Europids. Ethnicity needs to be considered when NAFLD is predicted using risk scores.
Asunto(s)
Enfermedades Cardiovasculares , Diabetes Mellitus Tipo 2 , Síndrome Metabólico , Enfermedad del Hígado Graso no Alcohólico , Anciano , Pueblo Asiatico , Enfermedades Cardiovasculares/diagnóstico por imagen , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/etnología , China/epidemiología , Diabetes Mellitus Tipo 2/diagnóstico por imagen , Diabetes Mellitus Tipo 2/epidemiología , Diabetes Mellitus Tipo 2/etnología , Femenino , Finlandia/epidemiología , Humanos , Masculino , Síndrome Metabólico/diagnóstico por imagen , Síndrome Metabólico/epidemiología , Síndrome Metabólico/etnología , Persona de Mediana Edad , Enfermedad del Hígado Graso no Alcohólico/diagnóstico por imagen , Enfermedad del Hígado Graso no Alcohólico/epidemiología , Enfermedad del Hígado Graso no Alcohólico/etnología , Factores de Riesgo , Población BlancaRESUMEN
Nonalcoholic fatty liver disease (NAFLD) has become the most common liver disease, and decreased fatty acid oxidation is one of the important contributors to NAFLD. Mitochondrial trifunctional protein α-subunit (MTPα) functions as a critical enzyme for fatty acid ß-oxidation, but whether dysregulation of MTPα is pathogenically connected to NAFLD is poorly understood. We show that MTPα is acetylated at lysine residues 350, 383, and 406 (MTPα-3K), which promotes its protein stability by antagonizing its ubiquitylation on the same three lysines (MTPα-3K) and blocking its subsequent degradation. Sirtuin 4 (SIRT4) has been identified as the deacetylase, deacetylating and destabilizing MTPα. Replacement of MTPα-3K with either MTPα-3KR or MTPα-3KQ inhibits cellular lipid accumulation both in free fatty acid (FFA)-treated alpha mouse liver 12 (AML12) cells and primary hepatocytes and in the livers of high-fat/high-sucrose (HF/HS) diet-fed mice. Moreover, knockdown of SIRT4 could phenocopy the effects of MTPα-3K mutant expression in mouse livers, and MTPα-3K mutants more efficiently attenuate SIRT4-mediated hepatic steatosis in HF/HS diet-fed mice. Importantly, acetylation of both MTPα and MTPα-3K is decreased while SIRT4 is increased in the livers of mice and humans with NAFLD. Our study reveals a novel mechanism of MTPα regulation by acetylation and ubiquitylation and a direct functional link of this regulation to NAFLD.
Asunto(s)
Ácidos Grasos/metabolismo , Proteínas Mitocondriales/metabolismo , Subunidad alfa de la Proteína Trifuncional Mitocondrial/química , Subunidad alfa de la Proteína Trifuncional Mitocondrial/metabolismo , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Sirtuinas/metabolismo , Acetilación , Animales , Modelos Animales de Enfermedad , Células HEK293 , Humanos , Metabolismo de los Lípidos , Lisina/metabolismo , Ratones , Oxidación-Reducción , Estabilidad Proteica , UbiquitinaciónRESUMEN
OBJECTIVE: To investigate the effect of pneumococcal vaccine polyvalent (pneumovax23) on defensin-2 gene expression in older rats. METHODS: Twenty older male Wistar rats (18-22 months) weighing (600 +/- 50) g were randomly allocated into two groups. The rats of experimental group were intraperitoneally injected with pneumovax23 0.2 ml/kg; the rats of control group were intraperitoneally injected with equivalent normal saline. Semiquantitive reverse transcription polymerase chain reaction (RT-PCR) was performed to detect beta-defensin-2 mRNA expression; beta-actin was used as the internal standard. RESULTS: The expression of beta-defensin-2 gene increased in the experimental group, as compared with that in the control group. CONCLUSION: Pneumovax23 can upregulate the expression of rBD-2 gene in the lung tissue and enhance the body local immunity. These experimental data indicate that Pneumovax23 can be used to enhance beta-defensin-2 and hence protect the old rats from pneumococci.
Asunto(s)
Pulmón/metabolismo , Vacunas Neumococicas/farmacología , beta-Defensinas/biosíntesis , Envejecimiento , Animales , Masculino , Neumonía/prevención & control , ARN Mensajero/biosíntesis , ARN Mensajero/genética , Distribución Aleatoria , Ratas , Ratas Wistar , beta-Defensinas/genéticaRESUMEN
OBJECTIVE: The ultrasound quantitative method for liver fat content (LFC) is a recent established method for non-invasive assessment of liver steatosis. Its use in clinical practice is further explored by investigating the quantitative relationships between LFC measured by quantitative ultrasonography and metabolic diseases in a middle-aged and elderly Chinese population. METHODS: Liver fat content was measured by the quantitative ultrasound method in 4,916 participants from the Shanghai Changfeng Community Study. The anthropometric and serum biochemical parameters related to glucose and lipid metabolism were detected for each participant. The carotid artery intima-media thickness (CIMT) was measured by ultrasonography. RESULTS: The LFC displayed a non-Gaussian and positively skewed distribution in the community population and was significantly correlated with body weight, serum glucose, lipid profile, and CIMT. The 95th percentile of LFC in the subgroup of participants without any metabolic disease was 10.8%, and a LFC ≥ 10% was correlated with remarkable increases in the risks for glucose and lipid metabolic diseases. CONCLUSIONS: The quantitative ultrasound method that was developed for measuring LFC was useful in a population study. A LFC ≥ 10% might help to identify the subjects with an increased risk for metabolic diseases.
Asunto(s)
Hígado Graso/diagnóstico por imagen , Enfermedades Metabólicas/etiología , Anciano , Anciano de 80 o más Años , Grosor Intima-Media Carotídeo , China/epidemiología , Estudios de Cohortes , Femenino , Glucosa/metabolismo , Humanos , Metabolismo de los Lípidos , Masculino , Persona de Mediana Edad , Factores de RiesgoRESUMEN
OBJECTIVES: A randomized, parallel controlled, open-label clinical trial was conducted to evaluate the effect of a botanic compound berberine (BBR) on NAFLD. METHODS: A randomized, parallel controlled, open-label clinical trial was conducted in three medical centers (NIH Registration number: NCT00633282). A total of 184 eligible patients with NAFLD were enrolled and randomly received (i) lifestyle intervention (LSI), (ii) LSI plus pioglitazone (PGZ) 15mg qd, and (iii) LSI plus BBR 0.5g tid, respectively, for 16 weeks. Hepatic fat content (HFC), serum glucose and lipid profiles, liver enzymes and serum and urine BBR concentrations were assessed before and after treatment. We also analyzed hepatic BBR content and expression of genes related to glucose and lipid metabolism in an animal model of NAFLD treated with BBR. RESULTS: As compared with LSI, BBR treatment plus LSI resulted in a significant reduction of HFC (52.7% vs 36.4%, p = 0.008), paralleled with better improvement in body weight, HOMA-IR, and serum lipid profiles (all p<0.05). BBR was more effective than PGZ 15mg qd in reducing body weight and improving lipid profile. BBR-related adverse events were mild and mainly occurred in digestive system. Serum and urine BBR concentrations were 6.99ng/ml and 79.2ng/ml, respectively, in the BBR-treated subjects. Animal experiments showed that BBR located favorably in the liver and altered hepatic metabolism-related gene expression. CONCLUSION: BBR ameliorates NAFLD and related metabolic disorders. The therapeutic effect of BBR on NAFLD may involve a direct regulation of hepatic lipid metabolism. TRIAL REGISTRATION: ClinicalTrials.gov NCT00633282.