Prevalence of non-alcoholic fatty liver disease and its association with lifestyle habits in adults in Chile: a cross-sectional study from the National Health Survey 2016-2017.

Non-alcoholic fatty liver disease (NAFLD) represents an excessive fat accumulation within the liver, usually associated with excess body weight. A liver biopsy is the gold standard for diagnosis, but it is inapplicable in population-based studies. In large populations, non-invasive methods could be used, which may also serve to identify potential protective factors. We aimed to (a) estimate NAFLD prevalence in the adult population in Chile by using non-invasive methods and (b) determine the association between the presence of NAFLD and lifestyle habits. The National Health Survey of Chile 2016­2017 was analysed. We included individuals aged 21­75 years, without infectious diseases nor risky alcohol consumption. NAFLD was detected by either fatty liver index (FLI; considers circulating TAG, circulating γ-glutamyl-transferase, BMI and waist circumference), lipid accumulation product (LAP; considers sex, circulating TAG and waist circumference) or their combination. Lifestyle habits were determined by questionnaires. We included 2774 participants, representative of 10 599 094 (9 831 644, 11 366 544) adults in Chile. NAFLD prevalence (95 % CI) was 39·4 % (36·2, 42·8) by FLI, 27·2 % (24·2, 30·4) by LAP and 23·5 % (20·7, 26·5) by their combination. The prevalence progressively increased with increasing BMI. Of note, less smoking and more moderate-vigorous physical activity and whole-grain consumption were associated with lower odds of having NAFLD, independently of BMI. At least one out of four adults in Chile is afflicted with NAFLD. Health promotion strategies focused on controlling excess body weight and promoting specific lifestyle habits are urgently required.

Association of the dopamine D2 receptor rs1800497 polymorphism with food addiction, food reinforcement, and eating behavior in Chilean adults.

PURPOSE: The regulation of food intake and body weight involves two interacting systems: (a) The homeostatic system (including biological regulators of hunger and satiety) and (b) the non-homeostatic system, (involving concepts of food reinforcement and food addiction). Studies have established a strong genetic component in eating behavior and obesity. The TaqI A1 polymorphism (rs1800497) has previously been associated with eating behavior, diminished dopamine D2 receptor (DRD2) density, higher body mass, and food reinforcement, but relations to food addiction remain unclear. AIM: To evaluate the association between the polymorphism rs1800497 with eating behavior, food reinforcement and food addiction in Chilean adults. METHODS: This cross-sectional study recruited a convenience sample of 97 obese, 25 overweight and 99 normal-weight adults (18-35 years). Anthropometric measurements were performed by standard procedures. Eating behavior was assessed using the: Yale Food Addiction Scale (YFAS), the Three Factor Eating Behavior Questionnaire and the Food Reinforcement Value Questionnaire (FRVQ). The DRD2 genotype (rs1800497) was determined by taqman assays. RESULTS: Twenty-two percentage of the participants met the criteria for food addiction. Food addiction was higher in women than men (26% vs 10.7%) and in obese compared to non-obese (40% vs 6%). There was no relationship between food addiction and DRD2 genotype. However when stratified by sex and nutritional status, obese female carriers of the A1 allele reported greater scores on emotional eating and snack food reinforcement compared to non-carriers. CONCLUSIONS: The DRD2 polymorphism is associated with some hedonic aspects of eating behavior, namely food reinforcement and emotional eating but not food addiction, and this association may be moderated by sex and obesity status, with obese women who are carriers of this genetic variant at higher risk. LEVEL OF EVIDENCE: Level V: evidence obtained from a cross-sectional descriptive study.

[The role of intestinal microbiota in the development of non-alcoholic fatty liver disease]. / Rol de la microbiota intestinal en el desarrollo del hígado graso no alcohólico.

Non-alcoholic fatty liver disease (NAFLD) encompasses a wide spectrum of hepatic pathologies ranging from simple steatosis (SS) to hepatocellular carcinoma. Intestinal microbiota (IM) is composed of trillions of microorganisms existing in the gut. It has 150 times more genes than the host. Changes in the composition and function of the IM are associated with different diseases, including NAFLD. In this condition, IM could have a pathogenic role through different mechanisms such as energy salvaging from food, an inflammatory stimulus, a modulation of the innate immune system, regulation of bile acid turnover, alteration of choline metabolism and increasing endogenous ethanol levels. This review is an update on the role of the intestinal microbiota in NAFLD and the possible mechanisms involved.

[Association between food addiction and nutritional status in Chilean college students]. / Asociación entre adicción a la comida y estado nutricional en universitarios chilenos.

BACKGROUND: High calorie foods, especially high in sugar and sodium may have an addictive potential. Experimental rats are able to develop symptoms and neurochemical changes, comparable to those observed in drug abuse, when they are exposed intermittently to sucrose. AIM: To evaluate the association between nutritional status and the prevalence of food addiction in Chilean college students. MATERIAL AND METHODS: Food addiction was assessed using the Yale Food Addiction Scale in 292 Chilean students aged 18-39 years (35% males). Height and weight were measured and body mass index (weight/height²) was calculated. RESULTS: Eleven percent of participants met the criteria for food addiction. Women had a higher prevalence than men (14.4% and 4.8%, respectively). Thirty percent of individuals with a body mass index over 30 kg/m² met the criteria for food addiction. CONCLUSIONS: In these Chilean students, food addiction was more prevalent in women and a higher prevalence was observed in obese individuals.

Relative fat mass as an estimator of body fat percentage in Chilean adults.

BACKGROUND/OBJECTIVE: The Relative Fat Mass (RFM) is an alternative index to body mass index (BMI) for estimating whole body fat percentage (BF%). Our aims were to determine the accuracy of the RFM for 1) identifying individuals with elevated BF% and, 2) estimating the BF% compared to Dual-energy X-ray absorptiometry (DXA) in a Chilean adult population. SUBJECTS/METHODS: Body composition was assessed by DXA in 270 healthy participants (125 women/145 men). Anthropometric measurements were assessed to calculate RFM and BMI. Receiver operating characteristic (ROC) curves were obtained to assess the sensitivity and specificity of both, RFM and BMI. Bland-Altman analysis between BF% measured by DXA vs. predicted BF% derived from RFM was performed to assess validity. Pearson´s correlation coefficients to analyze the association between BMI, RFM and DXA were also calculated. RESULTS: For RFM, the cut-off for elevated BF% was ≥22.7% for men and ≥32.4% for women and for BMI was ≥24.4 kg/m2 for men and ≥24.1 kg/m2 for women. The area under the ROC curve between RFM and BMI was not significantly different in men (0.970 vs. 0.959; p = 0.420) and women (0.946 vs. 0.942, p = 0.750). The Bland-Altman analysis showed that the estimation bias is more pronounced in men than in women. CONCLUSION: RFM is an accurate tool for identifying individuals with elevated BF%, although it was not as accurate as DXA for estimating the BF%. RFM may be an alternative method useful in primary care to select individuals for lifestyle counseling and in research to select patients for epidemiological studies.

Hepatic retinaldehyde dehydrogenases are modulated by tocopherol supplementation in mice with hepatic steatosis.

OBJECTIVES: An altered retinol metabolism might play a role in the development of nonalcoholic fatty liver disease (NAFLD). Tocopherols (TF) modulate metabolic pathways and have been proposed as a complementary treatment of obesity-induced metabolic alterations. Moreover, there is evidence suggesting that TF may modulate retinol metabolism. The aim of this study was to evaluate whether the dietary supplementation of α- and γ-TF modulates the expression of hepatic retinaldehyde dehydrogenases, RALDH1, RALDH2, and RALDH3 (involved in retinol metabolism) and, lipogenic factors sterol regulatory element binding protein-1c (SREBP-1c) and cluster differentiation 36 (CD36) in an animal model of diet-induced NAFLD. METHODS: Male C57BL/6J mice were divided into four groups: a control diet (CD) group (10% fat, 20% protein, 70% carbohydrates); a CD + TF group (α-tocopherol: 0.7 mg·kg·d-1, γ-tocopherol: 3.5 mg·kg·d-1); a high-fat diet (HFD) group (60% fat, 20% protein, 20% carbohydrates); and a HFD + TF group (0.01 mL·g body weight·d-1), for 12 wk. General parameters (body-adipose tissue weight, glucose-triacylglyceride serum levels), liver steatosis (histology, liver triacylglycerides content), and hepatic RALDH1, RALDH2, RALDH3, SREBP-1c and CD36 (qPCR, quantitative polymerase chain reaction; IHQ, immunohistochemistry) were measured. RESULTS: TF supplementation in HFD-fed mice decreased the presence of lipid vesicles (90%) and total lipid content (75%) and downregulated the expression of RALDH1, RALDH3, SREBP-1c, and CD36. CONCLUSIONS: The present study demonstrated that α- and γ-TF (1:5 ratio) might play a role in modulating retinol metabolism in the prevention of NAFLD induced by a HFD.

Higher hepatic advanced glycation end products and liver damage markers are associated with nonalcoholic steatohepatitis.

Advanced glycation end products (AGEs) may be associated with nonalcoholic fatty liver disease (NAFLD) from stimulation of oxidative stress, inflammation, and fibrosis. We hypothesized that patients with NAFLD would have a lower concentration of soluble AGEs receptor and higher quantity of serum and liver AGEs and an increase in hepatic smooth muscle actin alpha (α-SMA) and transforming growth factor beta 1 (TGF-ß1) compared with a control group. We compared the presence of hepatic and serum AGEs, AGE soluble receptor (sRAGE), and markers associated with hepatic damage between NAFLD patients and controls without disease. Histological characteristics, plasma biochemical parameters, serum AGEs, serum receptor sRAGE, and liver proteins (α-SMA, TGF-ß1, AGEs, immunohistochemistry) were assessed in participants aged 18 to 65 years, with NAFLD (simple steatosis [SS]: n = 7; steatohepatitis [NASH]: n = 15) and controls (n = 11). NASH patients presented higher glycated hemoglobin levels (%) (5.7; 5.4-6.3) compared with SS (5.4; 5.2-5.7) and controls (5.4; 5.3-5.5). The NAFLD activity score (NAS) for NASH patients was 4.9 ± 1.3; for SS patients, 2.0 ± 1.0. NASH patients showed higher hepatic AGEs, TGF-ß1, and α-SMA compared with SS and control groups. The NAS score indicates that patients with 5 to 8 had higher hepatic AGEs, TGF-ß1, and α-SMA compared with a NAS of 1 to 4 and 0. For α-SMA, a NAS of 1 to 4 was higher than NAS 0. No difference was found in serum AGEs and sRAGE between groups. Higher hepatic AGEs, TGF-ß1, and α-SMA were observed with increasing disease severity (according to NAS); therefore, endogenous liver AGEs may participate in hepatic damage progression.

Relationship Between Hepatic Gene Expression, Intestinal Microbiota, and Inferred Functional Metagenomic Analysis in NAFLD.

INTRODUCTION: We previously reported a lower fecal abundance of Ruminococcus spp., Faecalibacterium prausnitzii , and Coprococcus spp. in nonalcoholic fatty liver disease (NAFLD). In this article, we assess the associations between hepatic gene expression, the specific taxa, and bacterial pathways. METHODS: The relationships between hepatic genes that were differentially expressed in patients with NAFLD vs healthy controls (HC) and the abundance of these specific taxa were studied. Inferred functional metagenomic analysis using Piphillin was also performed to investigate associations with bacterial pathways. RESULTS: Fifteen patients with NAFLD and 6 HC participated. Of 728 hepatic genes examined, 176 correlated with the abundance of Ruminococcus spp., 138 with F. prausnitzii , and 92 with Coprococcus spp. For Ruminococcus spp., genes were enriched in gene ontology (GO) terms related to apoptotic process, response to external and cytokine stimuli, and regulation of signaling. Several genes related to the Kyoto Encyclopedia of Genes and Genomes pathway insulin resistance were correlated with F. prausnitzii . The hepatic genes associated with F. prausnitzii were enriched in GO terms related to cellular response to different stimuli, apoptotic process, and regulation of metabolic pathways. For Coprococcus spp., only the GO term response to external stimulus was enriched. There was a distinct pattern of associations between hepatic genes and bacterial taxa in NAFLD vs HC. For bacterial pathways, 65 and 18 hepatic genes correlated with bacterial metabolic functions in NAFLD and HC, respectively. DISCUSSION: Hepatic gene expression related to insulin resistance, inflammation, external stimuli, and apoptosis correlated with bacterial taxa. Patients with NAFLD showed a higher presence of bacterial pathways associated with lipid metabolism.

Enhancement in liver SREBP-1c/PPAR-alpha ratio and steatosis in obese patients: correlations with insulin resistance and n-3 long-chain polyunsaturated fatty acid depletion.

Sterol receptor element-binding protein-1c (SREBP-1c) and peroxisome proliferator-activated receptor-alpha (PPAR-alpha) mRNA expression was assessed in liver as signaling mechanisms associated with steatosis in obese patients. Liver SREBP-1c and PPAR-alpha mRNA (RT-PCR), fatty acid synthase (FAS) and carnitine palmitoyltransferase-1a (CPT-1a) mRNA (real-time RT-PCR), and n-3 long-chain polyunsaturated fatty acid (LCPUFA)(GLC) contents, plasma adiponectin levels (RIA), and insulin resistance (IR) evolution (HOMA) were evaluated in 11 obese patients who underwent subtotal gastrectomy with gastro-jejunal anastomosis in Roux-en-Y and 8 non-obese subjects who underwent laparoscopic cholecystectomy (controls). Liver SREBP-1c and FAS mRNA levels were 33% and 70% higher than control values (P<0.05), respectively, whereas those of PPAR-alpha and CPT-1a were 16% and 65% lower (P<0.05), respectively, with a significant 62% enhancement in the SREBP-1c/PPAR-alpha ratio. Liver n-3 LCPUFA levels were 53% lower in obese patients who also showed IR and hipoadiponectinemia over controls (P<0.05). IR negatively correlated with both the hepatic content of n-3 LCPUFA (r=-0.55; P<0.01) and the plasma levels of adiponectin (r=-0.62; P<0.005). Liver SREBP-1c/PPAR-alpha ratio and n-3 LCPUFA showed a negative correlation (r=-0.48; P<0.02) and positive associations with either HOMA (r=0.75; P<0.0001) or serum insulin levels (r=0.69; P<0.001). In conclusion, liver up-regulation of SREBP-1c and down-regulation of PPAR-alpha occur in obese patients, with enhancement in the SREBP-1c/PPAR-alpha ratio associated with n-3 LCPUFA depletion and IR, a condition that may favor lipogenesis over FA oxidation thereby leading to steatosis.

Cancer-related gene expression is associated with disease severity and modifiable lifestyle factors in non-alcoholic fatty liver disease.

OBJECTIVE: The aim of this study was to determine whether hepatic gene expression related to hepatocellular carcinoma (HCC) is associated with disease severity and modifiable lifestyle factors in non-alcoholic fatty liver disease (NAFLD). METHODS: In a cross-sectional study, the associations between hepatic gene expression and liver histology, insulin resistance, anthropometrics, diet, and physical activity were assessed in patients with non-alcoholic steatohepatitis (NASH; n = 19) or simple steatosis (SS; n = 20). In a group of patients with NASH, we then conducted a 1-y, single-arm, pilot study using ω-3 polyunsaturated fatty acid (PUFA) supplementation to determine whether changes in hepatic PUFA content would have a modulating effect on hepatic gene expression and would affect liver histology. RESULTS: In the cross-sectional study, histological features of disease severity correlated with AKR1B10, ANXA2, PEG10, SPP1, STMN2, MT1A, and MT1B in NASH and with EEF1A2, PEG10, and SPP1 in SS. In addition, PEG10, SPP1, ANXA2, and STMN2 expression correlated positively with insulin resistance in NASH. SPP1 and UBD correlated strongly with body mass index in SS. Associations between ENPP2, AKR1B10, SPP1, UBD, and waist circumference depended on sex and diagnosis. Several genes correlated with protein, fat, or carbohydrate intake. PEG10 correlated positively with physical activity in NASH and inversely with plasma vitamin C in both groups. Despite increased erythrocyte and hepatic ω-3 PUFA, supplementation did not alter hepatic gene expression and liver histology. CONCLUSIONS: HCC-related gene expression was associated with liver histology, body mass index, waist circumference, diet, and physical activity but was not affected by ω-3 PUFA supplementation.

Role of dietary α- and γ-tocopherol from Rosa mosqueta oil in the prevention of alterations induced by high-fat diet in a murine model.

OBJECTIVE: The aim of this study was to evaluate the contribution of tocopherols present in Rosa mosqueta oil (RM) in the prevention of high-fat diet (HFD)-induced alterations. METHODS: Male C57 BL/6 J mice (n = 9/group) were fed for 12 wk and divided into four groups: control (CD; 10% kcal fat, 20% kcal protein, 70% kcal carbohydrates); HFD (60% as fat, 20% kcal protein, 20% kcal carbohydrates); HFD + RM (0.01 mL/g body weight/d); and HFD + RM- without tocopherols (0.01 mL/g body weight/d). Parameters of obesity, liver steatosis (histology, triacylglycerols content), inflammation (adipose NLRP3 inflammasome, tumor necrosis factor-α and interleukin-1 ß expression, hepatic nuclear factor-κB) and oxidative stress (hepatic Nrf2 activation, carbonylated proteins) were evaluated. RESULTS: Liver steatosis, inflammatory, and oxidative stress parameters were significantly (P < 0.05) increased in the HFD + RM- compared with the HFD + RM, with no differences between HFD and HFD + RM-. CONCLUSION: The present study suggests that α- and γ-tocopherols from RM may have an important role in the prevention of alterations induced by HFD.

Situación Nutricional de embarazadas y lactantes haitianos atendidos en el CESFAM "Los Castaños" de la comuna de La Florida, Región Metropolitana, Chile

En Chile, al 31 de diciembre del 2020 un 12,5% de los extranjeros eran de nacionalidad haitiana. Se desconoce el estado nutricional (EN) en embarazadas y lactantes; así como también la prevalencia de lactancia materna exclusiva (LME) de la población haitiana en Chile. Los objetivos de este trabajo fueron comparar: (i) el EN de embarazadas haitianas y chilenas, (ii) el EN de lactantes y (iii) la duración de la LME en hijos de madres haitianas y chilenas. Para esto se analizó la base de datos de la población haitiana y chilena atendidos entre los años 2016-2019 en el Centro de Salud Familiar (CESFAM) "Los Castaños" ubicado en la comuna de La Florida. En la etapa pre-gestacional, las embarazadas haitianas presentaron mayor prevalencia de bajo peso en comparación a embarazadas chilenas (p= 0,0003), mientras que al término del embarazo presentaron una mayor prevalencia de estado nutricional normal (p= 0,0001) y menor prevalencia de obesidad (p= 0,0001). Respecto al estado nutricional de los lactantes, sólo se observaron diferencias en el primer mes de vida, donde un 82% de los lactantes haitianos tenían un EN normopeso en comparación al 24% en los lactantes chilenos (p= 0,0001). No se observaron diferencias significativas en la prevalencia de LME hasta los 6 meses entre lactantes haitianos y chilenos (35,3% vs 30%, respectivamente). Es importante mencionar que ninguno de los dos grupos de lactantes cumplió con la meta establecida por la Organización Mundial de la Salud (OMS) que propone LME en los primeros seis meses de vida hasta al menos 50%. En conclusión, se evidencian diferencias en el EN de las embarazadas y lactantes de ambos países, mientras que la prevalencia de LME en ambos grupos fue similar.

In Chile, until December 31st, 2020, 12.5% of foreign residents were from Haiti. The nutritional status (NS) in pregnant women and infants is unknown; as well as the prevalence of exclusive breastfeeding (EBF) of the Haitian population residing in Chile. This study aimed to compare: (i) the NS of Haitian and Chilean pregnant women, (ii) the NS of infants, and (iii) the duration of EBF in children of Haitian and Chilean mothers. We analyzed the database of the Haitian and Chilean population attended between the years 2016-2019 at the Primary Care Health Center (CESFAM) "Los Castaños" located in the commune of La Florida. During the pregestational stage, the Haitian pregnant women had a higher prevalence of low weight compared to the Chilean pregnant women (p= 0,0003), whereas, at the end of the pregnancy, they had a higher prevalence of normal nutritional status (p= 0,0001) and a lower prevalence of obesity and a tendency at the end of pregnancy. Whereas at the end of the pregnancy, Chilean women had a higher prevalence of obesity. Regarding the nutritional status of the infants, differences were only observed in the first month of life, where 82% of Haitian infants had a normal weight compared to 24% of Chilean infants (p= 0.0001). No significant differences were observed in the prevalence of EBF up to 6 months between Haitian and Chilean infants (35.3% vs. 30%, respectively). It is important to mention that neither of the two groups of infants met the goal established by the World Health Organization (WHO) that proposes EBF for the first six months of life up to at least 50%. In conclusion, there are differences in the NE of pregnant and lactating women in both countries, while the prevalence of EBF in both groups was similar.

Altered hepatic genes related to retinol metabolism and plasma retinol in patients with non-alcoholic fatty liver disease.

Non-alcoholic fatty liver disease (NAFLD), especially non-alcoholic steatohepatitis (NASH) is a chronic liver disease commonly associated with hepatic fibrosis. NASH patients have an increased risk for hepatocellular carcinoma (HCC). An altered retinol metabolism is one of the pathways involved in the process of hepatic fibrosis, and enzymes involved in retinol metabolism have been associated with HCC. We aimed to determine the association between plasma retinol levels and hepatic expression of genes related to retinol metabolism, as well as to assess the hepatic expression of transcription factors regulated by retinoic acid in patients with NAFLD. Cross-sectional study where hepatic gene expression (Illumina microarray) and plasma retinol levels (HPLC) were measured in 17 patients with simple steatosis (SS), 15 with NASH, and 22 living liver donors (LD) as controls. Plasma retinol levels were higher in SS (1.53 ± 0.44 µmol/L) and NASH (1.51 ± 0.56 µmol/L) compared to LD (1.21 ± 0.38 µmol/L; p<0.05). AKR1B10 was highly overexpressed in NASH compared to SS (+6.2-fold) and LD (+9.9-fold; p = 4.89E-11). Retinaldehyde dehydrogenase 1 family, member A2 (ALDH1A2) and retinaldehyde dehydrogenase 1 family, member A3 (ALDH1A3), key enzymes for retinoic acid synthesis, were underexpressed in SS (-1.48 and -2.3-fold, respectively) and NASH (-1.47 and -2.6-fold, respectively) versus LD. In NASH, hepatic ALDH1A2 and ALDH1A3 were underexpressed and inversely correlated with plasma retinol levels, which may reduce retinoic acid in the liver. This, in addition to changes in expression of other genes involved in retinol metabolism, suggests a role for altered retinol homeostasis in NASH.

Rol de la microbiota intestinal en el desarrollo del hígado graso no alcohólico / The role of intestinal microbiota in the development of non-alcoholic fatty liver disease

Non-alcoholic fatty liver disease (NAFLD) encompasses a wide spectrum of hepatic pathologies ranging from simple steatosis (SS) to hepatocellular carcinoma. Intestinal microbiota (IM) is composed of trillions of microorganisms existing in the gut. It has 150 times more genes than the host. Changes in the composition and function of the IM are associated with different diseases, including NAFLD. In this condition, IM could have a pathogenic role through different mechanisms such as energy salvaging from food, an inflammatory stimulus, a modulation of the innate immune system, regulation of bile acid turnover, alteration of choline metabolism and increasing endogenous ethanol levels. This review is an update on the role of the intestinal microbiota in NAFLD and the possible mechanisms involved.

Childhood obesity and eating behaviour.

The prevalence of childhood obesity has increased substantially in the recent decade as a result of the reduction in physical activity and the availability of high-fat and high-energy-density foods which the paediatric population faces daily. Although children are highly exposed to these foods, there is a wide variation in body weight, suggesting the presence of different patterns of response to an "obesogenic" environment. This wide variability from the point of view of eating behaviour involves a number of social issues (e.g., food availability, cost) as well as genuine behavioural traits such as the response to satiety, energy compensation, eating rate, responsiveness to food, food reward and dietary preferences. This article reviews the main physiological variables related to energy intake affecting eating behaviour in the paediatric population.

[Fructose consumption and its health implications; fructose malabsorption and nonalcoholic fatty liver disease]. / Consumo de fructosa y sus implicaciones para la salud; malabsorción de fructosa e hígado graso no alcohólico.

UNLABELLED: Fructose intake has increased considerably in recent years, especially in the form high fructose corn syrup, due its high sweetening power. Several studies have associated high intake of fructose to metabolic alterations, as nonalcoholic fatty liver disease and fructose malabsorption, among other pathologies. This review aims to update about the effect of high intake of fructose in the liver and intestine, mainly associated with processed foods with added fructose. METHODS: An updated literature search was conducted using databases (Pubmed, Scopus and SciELO), selecting articles published after the year 2000, resulting from the keywords "fructose intake, fructose intolerance, nonalcoholic fatty liver and fructose, fructose malabsorption" RESULTS: Of 735 articles initially retrieved, 78 met the inclusion criteria. CONCLUSIONS: Fructose consumption has increased in recent decades, especially due to increased consumption of sweetened beverages and processed foods with added fructose. High fructose intake has been associated to pathologies as NAFLD and fructose malabsorption.

La ingesta de fructosa se ha incrementado considerablemente en los últimos años, especialmente bajo la forma de jarabe de maíz alto en fructosa, debido a su gran poder edulcorante. Diversos estudios, han asociado su elevado consumo con alteraciones metabólicas, hígado graso no alcohólico y malabsorción de fructosa, entre otras patologías. Esta revisión tiene como objetivo actualizar acerca del efecto de la alta ingesta de fructosa en el hígado e intestino, asociada principalmente a alimentos procesados con fructosa agregada. Métodos: Para la búsqueda bibliográfica se utilizaron las bases de datos de Pubmed, Scopus y Scielo, seleccionando aquellos artículos publicados después del año 2000 y resultantes de las palabras claves "fructose intake, high fructose corn syrup, nonalcoholic fatty liver and fructose, fructose malabsorption, fructose intolerance/metabolism". Resultados: La búsqueda arrojó 735 publicaciones de las cuales 78 cumplieron con los criterios de inclusión. Conclusiones: El consumo de fructosa ha aumentado en las últimas décadas, especialmente a través de bebidas endulzadas y productos alimentarios con fructosa agregada. La alta ingesta de fructosa tiene un impacto a nivel intestinal y hepático, asociándose a patologías como hígado graso no alcohólico y malabsorción de fructosa.

Misregulation of PPAR Functioning and Its Pathogenic Consequences Associated with Nonalcoholic Fatty Liver Disease in Human Obesity.

Nonalcoholic fatty liver disease in human obesity is characterized by the multifactorial nature of the underlying pathogenic mechanisms, which include misregulation of PPARs signaling. Liver PPAR-α downregulation with parallel PPAR-γ and SREBP-1c up-regulation may trigger major metabolic disturbances between de novo lipogenesis and fatty acid oxidation favouring the former, in association with the onset of steatosis in obesity-induced oxidative stress and related long-chain polyunsaturated fatty acid n-3 (LCPUFA n-3) depletion, insulin resistance, hypoadiponectinemia, and endoplasmic reticulum stress. Considering that antisteatotic strategies targeting PPAR-α revealed that fibrates have poor effectiveness, thiazolidinediones have weight gain limitations, and dual PPAR-α/γ agonists have safety concerns, supplementation with LCPUFA n-3 appears as a promising alternative, which achieves both significant reduction in liver steatosis scores and a positive anti-inflammatory outcome. This latter aspect is of importance as PPAR-α downregulation associated with LCPUFA n-3 depletion may play a role in increasing the DNA binding capacity of proinflammatory factors, NF-κB and AP-1, thus constituting one of the major mechanisms for the progression of steatosis to steatohepatitis.

Up-regulation of PPAR-gamma mRNA expression in the liver of obese patients: an additional reinforcing lipogenic mechanism to SREBP-1c induction.

INTRODUCTION: Triglyceride accumulation in the liver is an early feature in the development of nonalcoholic fatty liver disease (NAFLD) associated with human obesity, which is a multifactorial syndrome and whose underlying mechanisms are beginning to be understood. OBJECTIVES: Liver peroxisome proliferator-activated receptor-γ (PPAR-γ) mRNA expression was measured as a signaling mechanism related to steatosis in obese patients with NAFLD. METHODS: Liver PPAR-γ and sterol receptor element-binding protein 1c (SREBP-1c) mRNA (real-time RT-PCR), serum total adiponectin (RIA), and high molecular weight (HMW)-adiponectin (ELISA) levels, and insulin resistance (IR) evolution (homeostasis model assessment-IR) were determined in 22 obese NAFLD patients (16 with steatosis and six with steatohepatitis) who underwent subtotal gastrectomy with gastrojejunal anastomosis in Roux-en-Y and 16 nonobese subjects who underwent laparoscopic cholecystectomy (controls). RESULTS: Liver PPAR-γ mRNA levels were 112 and 188% higher (P < 0.05) than control values in obese patients with steatosis and steatohepatitis, respectively, who also exhibited 70 and 62% increases in those of SREBP-1c, concomitantly with IR and lower levels of serum total adiponectin and HMW-adiponectin (P < 0.05). Liver PPAR-γ expression showed positive associations with SREBP-1c mRNA levels (r = 0.86; P < 0.0001), serum insulin levels (r = 0.39; P < 0.01), and homeostasis model assessment-IR (r = 0.60; P < 0.0001), and negative correlations with total adiponectin (r = -0.37; P < 0.01) and HMW-adiponectin (r = -0.51; P < 0.001) levels in serum. CONCLUSIONS: PPAR-γ is up-regulated in the liver of obese patients with NAFLD, representing an additional reinforcing lipogenic mechanism to SREBP-1c induction in the development of hepatic steatosis.