cholecalciferol and Non-alcoholic-Fatty-Liver-Disease

Vitamin D (calciferol) is a fat-soluble vitamin that has a significant role in phospho-calcium metabolism, maintaining normal calcium levels and bone health development. The most important compounds of vitamin D are cholecalciferol (vitamin D3, or VD3) and ergocalciferol (vitamin D2, or VD2). Besides its major role in maintaining an adequate level of calcium and phosphate concentrations, vitamin D is involved in cell growth and differentiation and immune function. Recently, the association between vitamin D deficiency and the progression of fibrosis in chronic liver disease (CLD) was confirmed, given the hepatic activation process and high prevalence of vitamin D deficiency in these diseases. There are reports of vitamin D deficiency in CLD regardless of the etiology (chronic viral hepatitis, alcoholic cirrhosis, non-alcoholic fatty liver disease, primary biliary cirrhosis, or autoimmune hepatitis). Vitamin D binding protein (VDBP) is synthesized by the liver and has the role of binding and transporting vitamin D and its metabolites to the target organs. VDBP also plays an important role in inflammatory response secondary to tissue damage, being involved in the degradation of actin. As intense research during the last decades revealed the possible role of vitamin D in liver diseases, a deeper understanding of the vitamin D, vitamin D receptors (VDRs), and VDBP involvement in liver inflammation and fibrogenesis could represent the basis for the development of new strategies for diagnosis, prognosis, and treatment of liver diseases. This narrative review presents an overview of the evidence of the role of vitamin D and VDBP in CLD, both at the experimental and clinical levels.

Topics: Actins; Calcium; Cholecalciferol; Ergocalciferols; Humans; Liver Diseases; Non-alcoholic Fatty Liver Disease; Phosphates; Receptors, Calcitriol; Vitamin D; Vitamin D Deficiency; Vitamin D-Binding Protein; Vitamins

Vitamin D deficiency is often reported in people with chronic liver diseases. Therefore, improving vitamin D status could have a beneficial effect on people with chronic liver diseases.. To assess the beneficial and harmful effects of vitamin D supplementation in people with chronic liver diseases.. We searched The Cochrane Hepato-Biliary Group Controlled Trials Register, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, Science Citation Index Expanded, and Conference Proceedings Citation Index - Science. We also searched databases of ongoing trials and the World Health Organization International Clinical Trials Registry Platform. We scanned bibliographies of relevant publications and asked experts and pharmaceutical companies for additional trials. All searches were up to January 2017.. Randomised clinical trials that compared vitamin D at any dose, duration, and route of administration versus placebo or no intervention in adults with chronic liver diseases. Vitamin D could have been administered as supplemental vitamin D (vitamin D. We used standard methodological procedures expected by The Cochrane Collaboration. We contacted authors of the trials to ask for missing information. We conducted random-effects and fixed-effect meta-analyses. For dichotomous outcomes, we calculated risk ratios (RRs), and for continuous outcomes, we calculated mean differences (MD), both with 95% confidence intervals (CI) and Trial Sequential Analyses-adjusted CIs. We calculated Peto odds ratio (OR) for rare events. We considered risk of bias in domains to assess the risk of systematic errors. We conducted Trial Sequential Analyses to control the risk of random errors. We assessed the quality of the evidence with GRADE.. We included 15 randomised clinical trials with 1034 participants randomised. All trials had a parallel group design. Nine trials were conducted in high-income countries and six trials in middle-income countries. All trials were at high risk of bias. Six trials included participants with chronic hepatitis C, four trials included participants with liver cirrhosis, four trials included participants with non-alcoholic fatty liver disease, and one trial included liver transplant recipients. All included trials reported the baseline vitamin D status of participants. Participants in six trials had baseline 25-hydroxyvitamin D levels at or above vitamin D adequacy (20 ng/mL), while participants in the remaining nine trials were vitamin D insufficient (less than 20 ng/mL). All trials administered vitamin D orally. Mean duration of vitamin D supplementation was 0.5 years and follow-up was 0.6 years. Eleven trials (831 participants; 40% women; mean age 52 years) tested vitamin D. We are uncertain as to whether vitamin D supplements in the form of vitamin D

Topics: Administration, Oral; Calcitriol; Cause of Death; Cholecalciferol; Chronic Disease; Ergocalciferols; Female; Hepatitis C, Chronic; Humans; Hydroxycholecalciferols; Liver Cirrhosis; Liver Diseases; Liver Transplantation; Male; Middle Aged; Non-alcoholic Fatty Liver Disease; Randomized Controlled Trials as Topic; Vitamin D; Vitamin D Deficiency; Vitamins

Nonalcoholic fatty liver disease (NAFLD) and vitamin D3 deficiency are two highly prevalent pathologic conditions worldwide that share several cardiometabolic risk factors. In addition to its traditional calcium-related effects on the skeleton, vitamin D3 deficiency has now been recognized to exert nonskeletal adverse effects on several other organ systems. Accumulating epidemiological evidence suggests that low levels of serum 25-hydroxyvitamin D3 are associated with the presence and severity of NAFLD, independently of several potential confounders, including features of the metabolic syndrome. The molecular mechanisms of this association remain incompletely understood. A variety of biologically plausible mechanisms may mediate a hepato-protective role for the active metabolite of vitamin D3. 1α,25-dihydroxyvitamin D3 modulates the insulin signaling pathway/insulin resistance, suppresses fibroblast proliferation and collagen production, exerts anticoagulant and profibrinolytic effects, and modulates macrophage activity and inflammatory cytokine generation. Overall, the high prevalence of vitamin D3 deficiency and the plausible biological mechanisms linking this to NAFLD suggest that treatment of vitamin D3 deficiency to prevent and/or treat NAFLD is a promising field to explore. Large placebo-controlled randomized clinical trials are urgently needed to determine whether vitamin D3 supplementation could have any potential benefit in reducing the development and progression of NAFLD.

Topics: Adipose Tissue; Bile; Bile Acids and Salts; Cholecalciferol; Fatty Liver; Humans; Immunologic Factors; Insulin Resistance; Intestinal Mucosa; Models, Biological; Non-alcoholic Fatty Liver Disease; Risk Factors; Signal Transduction; Vitamin D Deficiency

Non-alcoholic fatty liver disease (NAFLD) is a common chronic liver metabolic disease affecting millions globally. This study aimed to assess the safety and efficacy of a high oral loading dose of cholecalciferol supplement on NAFLD patients and to investigate its potential role on serum inflammatory biomarkers.. One hundred patients with NAFLD and type 2 diabetes mellitus were involved in the study. Eligible patients were randomized among two equal groups. Group 1 received the standard conventional therapy in addition to a placebo. Group 2 received the conventional therapy plus cholecalciferol for 4 months. The improvement in the patients' glycaemic control parameters, liver function tests, lipid profile, and serum 25-hydroxy vitamin D at the end of the study was set as a primary outcome. The secondary outcome was the decrease in steatosis grade in the ultrasound and high-sensitivity C-reactive protein (hs-CRP), tumor necrosis factor-alpha (TNF-α), signal transducer and activator of factor-3 (STAT-3), nitric oxide (NO), malondialdehyde (MDA), and hepassocin serum levels at the end of the study.. Group 2 revealed a significant reduction in the serum levels of lipid profile measures, hs-CRP, alanine aminotransferase (ALT), STAT-3, NO, hepassocin, and MDA compared to the baseline and group 1 results. Whereas group 1 did not show these significant changes. Both groups observed no significant changes in glycemic index, TNF-α, aspartate aminotransferase (AST), and albumin levels.. Cholecalciferol is recommended as additional therapy to modulate lipid peroxidation and systemic inflammation alongside other NAFLD therapies.

Topics: C-Reactive Protein; Cholecalciferol; Diabetes Mellitus, Type 2; Double-Blind Method; Humans; Non-alcoholic Fatty Liver Disease; Tumor Necrosis Factor-alpha

The present study aimed to investigate fish oil plus vitamin D. Using multivariable-adjusted general linear model, there were significant net reductions in serum alanine aminotransferase (ALT), and triacylglycerol (TAG) and TNF-α levels in the FO + D and FO groups, compared with the control group (P < 0.05). The supplemental FO + D also showed significant reductions in insulin (- 1.58 ± 2.00 mU/L vs. - 0.63 ± 1.55 mU/L, P = 0.050) and IL-1β (- 6.92 ± 7.29 ng/L vs. 1.06 ± 5.83 ng/L, P < 0.001) in comparison with control group. Although there were no significant differences between FO + D and FO groups regarding biochemical parameters, supplemental FO + D showed decreases in ALT (from 26.2 ± 13.5 U/L to 21.4 ± 9.6 U/L, P = 0.007), aspartate aminotransferase (AST, from 22.5 ± 7.0 U/L to 20.2 ± 4.0 U/L, P = 0.029), HOMA-IR (from 3.69 ± 1.22 to 3.38 ± 1.10, P = 0.047), and TNF-α (from 0.43 ± 0.38 ng/L to 0.25 ± 0.42 ng/L, P < 0.001) levels following the intervention.. The present study demonstrated that groups supplemented with FO + D and FO had similar beneficial effects on biomarkers of hepatocellular damage and plasma TAG levels in subjects with NAFLD, while in the FO + D group, there were some suggestive additional benefits compared with FO group on insulin levels and inflammation.. ChiCTR1900024866.

Topics: Biomarkers; Cholecalciferol; Dietary Supplements; Docosahexaenoic Acids; Eicosapentaenoic Acid; Fish Oils; Humans; Insulin; Middle Aged; Non-alcoholic Fatty Liver Disease; Triglycerides; Tumor Necrosis Factor-alpha

Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease in the world with no definite treatment. Insulin resistance (IR) and low serum vitamin D are closely linked to NAFLD. Since there is no comparative study on the effect of calcitriol with cholecalciferol on NAFLD based on homeostasis model of insulin resistance (HOMA-IR) as an IR indicator, so we designed this research.. A double blind randomized clinical trial was conducted on patients with NAFLD with concomitant vitamin D deficiency/insufficiency at two referral tertiary teaching medical centers, from July 2017 to January 2019. Patients were randomly divided into two groups: calcitriol (1 mcg/day) and cholecalciferol (50,000 IU/week) for 8 weeks. Before and after the intervention, anthropometric and laboratory data were measured and HOMA-IR was calculated for each patient.. 54 patients completed the trial. In total, calcitriol supplementation improved serum insulin levels as well as IR based on the HOMA-IR index, significantly compared to the cholecalciferol group. HOMA-IR decreased 1.8 times more in patients receiving calcitriol than in those receiving cholecalciferol, which was clinically meaningful. The observed changes were more pronounced in patients with higher baseline body mass index. Moreover, calcitriol was more associated with a significant decrease in liver enzymes and cholesterol levels comparing to cholecalciferol.. Based on the findings of this study, the use of calcitriol supplementation significantly reduced HOMA-IR as an IR indicator in NAFLD patients, compared to cholecalciferol. To confirm this findings, further studies with larger sample sizes are recommended.

Topics: Adult; Calcitriol; Cholecalciferol; Dietary Supplements; Double-Blind Method; Female; Humans; Insulin Resistance; Iran; Male; Non-alcoholic Fatty Liver Disease; Treatment Outcome; Vitamins

Bariatric patients often suffer from vitamin D deficiency (VDD), and both, morbid obesity and VDD, are related to non-alcoholic fatty liver disease. However, limited data are available regarding best strategies for treating VDD, particularly, in bariatric patients undergoing omega-loop gastric bypass (OLGB). Therefore, we examined the efficacy and safety of a forced vitamin D dosing regimen and intervention effects in liver fibrotic patients.. Compared with control group, higher increase of 25(OH)D (67.9 (21.1) vs. 55.7 nmol/L (21.1); p = 0.049) with lower prevalence of secondary hyperparathyroidism (10 vs. 24 %; p = 0.045) was observed in intervention group. No (serious) adverse events related to study medication were found. The loading dose regimen was more effective in increasing 25(OH)D in patients with significant liver fibrosis while this was not the case for conventional supplementation (placebo with maintenance dose) (71.5 (20.5) vs. 22.5 nmol/L (13.8); p = 0.022; n = 14).. Our findings indicate that a high vitamin D

Topics: Adult; Cholecalciferol; Dietary Supplements; Double-Blind Method; Female; Gastric Bypass; Humans; Hyperparathyroidism, Secondary; Liver Cirrhosis; Male; Middle Aged; Non-alcoholic Fatty Liver Disease; Obesity, Morbid; Postoperative Period; Prevalence; Vitamin D; Vitamin D Deficiency; Vitamins; Weight Loss

Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in Western countries. A meta-analysis has confirmed decreased serum 25-hydroxyvitamin D levels in NAFLD patients. This intervention study investigates whether vitamin D correction ameliorates hepatic steatosis.. We prospectively recruited 40 patients from an outpatient liver clinic with vitamin D deficiency (serum 25-hydroxyvitamin D < 20 ng/ml). Controlled attenuation parameter (CAP) during transient elastography quantified hepatic steatosis. Patients with significant liver fat accumulation were included, which was defined by a CAP value >/= 280 dB/m. Patients received 20,000 IU vitamin D/week for six months, while vitamin D status, liver function tests (LFTs), CAP and body composition were monitored.. The cohort comprised 47.5% women (age 54.9 +/- 12.1 years; BMI 29.5 +/- 3.0 kg/m2). Mean serum vitamin D level was 11.8 +/- 4.8 ng/ml. CAP decreased significantly from baseline (330 +/- 32 vs. 307 +/- 41 dB/m) during supplementation (P = 0.007). A mean CAP reduction relative to baseline was demonstrated at four weeks and three and six months: -5.3 +/- 13.8%; -6.0 +/- 14.6% and -6.4 +/- 13.0%, respectively. During these time points, restoration of serum vitamin D levels was observed (34.6 +/- 12.9, 36.3 +/- 10.2, 34.8 +/- 9.8 ng/ml; P < 0.0001). Liver function tests and body composition remained unchanged.. Hepatic steatosis, as assessed by CAP, significantly improves after only 4 weeks of vitamin D correction. Hepatic steatosis is a dynamic process, that can be monitored in the short-term using such non-invasive methods.

Topics: Adult; Aged; Ambulatory Care Facilities; Biomarkers; Cholecalciferol; Dietary Supplements; Elasticity Imaging Techniques; Female; Germany; Humans; Liver; Male; Middle Aged; Non-alcoholic Fatty Liver Disease; Prospective Studies; Risk Factors; Time Factors; Treatment Outcome; Vitamin D; Vitamin D Deficiency

Non-alcoholic fatty liver disease (NAFLD) is the most common hepatic disorder worldwide, reaching prevalence up to 90 % in obese patients with type 2 diabetes (T2D), and representing an independent risk factor for cardiovascular mortality. Furthermore, the coexistence of T2D and NAFLD leads to higher incidence of diabetes' complications and additive detrimental liver outcomes. The existence of a close association between NAFLD and hypovitaminosis D, along with the anti-inflammatory and insulin-sensitizing properties of vitamin D, have been largely described, but vitamin D effects on hepatic fat content have never been tested in a randomized controlled trial. We assessed the efficacy and safety of 24-week oral high-dose vitamin D supplementation in T2D patients with NAFLD.. This randomized, double-blind, placebo-controlled trial was carried out at the Diabetes Centre of Sapienza University, Rome, Italy, to assess oral treatment with cholecalciferol (2000 IU/day) or placebo in T2D patients with NAFLD. The primary endpoint was reduction of hepatic fat fraction (HFF) measured by magnetic resonance; as hepatic outcomes, we also investigated changes in serum transaminases, CK18-M30, N-terminal Procollagen III Propeptide (P3NP) levels, and Fatty Liver Index (FLI). Secondary endpoints were improvement in metabolic (fasting glycaemia, HbA1c, lipids, HOMA-IR, HOMA-β, ADIPO-IR, body fat distribution) and cardiovascular (ankle-brachial index, intima-media thickness, flow-mediated dilatation) parameters from baseline to end of treatment.. Sixty-five patients were randomized, 26 (cholecalciferol) and 29 (placebo) subjects completed the study. 25(OH) vitamin D significantly increased in the active treated group (48.15 ± 23.7 to 89.80 ± 23.6 nmol/L, P < 0.001); however, no group differences were found in HFF, transaminases, CK18-M30, P3NP levels or FLI after 24 weeks. Vitamin D neither changed the metabolic profile nor the cardiovascular parameters.. Oral high-dose vitamin D supplementation over 24 weeks did not improve hepatic steatosis or metabolic/cardiovascular parameters in T2D patients with NAFLD. Studies with a longer intervention period are warranted for exploring the effect of long time exposure to vitamin D.. This trial was approved on July 2011 by the Ethics Committee of Policlinico Umberto I, Sapienza University of Rome, Italy, and registered at www.clinicaltrialsregister.eu number 2011-003010-17.

Topics: Administration, Oral; Cholecalciferol; Diabetes Mellitus, Type 2; Dietary Supplements; Double-Blind Method; Female; Humans; Italy; Male; Middle Aged; Non-alcoholic Fatty Liver Disease; Risk Factors

Damage-associated molecular patterns released upon hepatocyte injury ensuing non-alcoholic steatohepatitis (NASH) can stimulate innate immunity by activating NOD-like receptor family pyrin domain-containing protein 3 (NLRP3) inflammasome, thereby triggering pro-inflammatory cascades in the liver. Aberrant NLRP3 activation allied to compromised autophagic clearance of its components contributes to the progression of multiple inflammatory diseases. Such intricate interplay, however, was not fully deciphered in NASH. Prior studies have illuminated the ability of vitamin D3 to temper inflammasome activation in several contexts, prompting us to probe the impact of vitamin D3, particularly its active form, calcitriol (CAL), on NLRP3 overactivation in a high-fat diet (HFD)-based NASH model and its potential dependence on autophagy. Hydroxychloroquine (HCQ), an autophagy inhibitor, was co-administered with CAL to examine the likely modulation of the NLRP3/autophagy crosstalk. Our results showed that treatment with CAL countervailed the histopathological derangement reported in the livers of HFD-fed mice that paralleled a restoration of vitamin D receptor gene expression and reduction in sterol regulatory element binding protein 1c levels. Moreover, p62 was curtailed with CAL treatment indicating autophagy induction. CAL also prompted a reduction in NLRP3, caspase-1, gasdermin D, and IL-18 protein levels along with the apoptosis-associated speck-like protein (ASC) gene expression. Treatment with CAL also reduced IL-1β and caspase-3 immunoreactivities compared to control. Intriguingly, CAL modulatory effects on inflammasome activation were curbed in the group that received HCQ, suggesting a potential autophagy dependency. Accordingly, the current study suggests that CAL was capable of ameliorating NASH via inhibiting NLRP3 inflammasome activation in an autophagy-dependent manner.

Topics: Animals; Autophagy; Calcitriol; Cholecalciferol; Inflammasomes; Mice; NLR Family, Pyrin Domain-Containing 3 Protein; Non-alcoholic Fatty Liver Disease

Nonalcoholic fatty liver is one of the most common forms of liver disease and role of microRNAs (miRNAs) on this illness is currently unclear. It was aimed to evaluate the predictive role of circulating miR-33a and mir-200c on high fructose corn syrup (HFCS)-induced fatty liver and vitamin D3 supplementation-related hepatic changes.. Twenty-four rats were randomized into three groups: sham (n = 8), experimental fatty liver group (n = 8), and fatty liver + vitamin D3 supplementation group (n = 8). In the treatment group, 10 µg/kg/week of vitamin D3 was given by orogastric tube weekly for 4 weeks in addition to a high fructose diet. Serum AST, ALT, TNF-α, and MDA levels were tested. Liver tissue samples were examined using hematoxylin/eosin, periodic acid-Schif (PAS) and Masson's Trichrome staining. Circulating miR-33a and mir-200c were quantified by qRT-PCR method. Moreover, in silico analyses were accomplished.. In the vitamin D3 group, results of biochemical parameters were significantly different than those of the fatty liver group (p < 0.001). Moreover, significant differences in serum levels of circulating miR-33a and mir-200c were identified among all groups (p < 0.05). Finally, more favorable histopathological changes were noticed in the vitamin D3 supplementation group. The expressions of Ki-67 were also considerably reduced in the vitamin D3 group. According to KEGG pathway analysis, mir-33a and mir-200c were found to play a common role in the Hippo signaling pathway, lysine degradation, and protein processing.. Our current experimental fatty liver study showed that, in a specified dose, vitamin D3 supplementation could alleviate adverse undesirable hepatic effects of HFCS via miR-33a and mir-200c.

Topics: Animals; Biomarkers; Cholecalciferol; Dietary Supplements; High Fructose Corn Syrup; MicroRNAs; Non-alcoholic Fatty Liver Disease; Rats; Vitamin D; Vitamins

Topics: Cholecalciferol; COVID-19; Female; Humans; Metabolic Syndrome; Non-alcoholic Fatty Liver Disease; Pandemics; SARS-CoV-2; Vitamin D; Vitamin D Deficiency; Volunteers

Topics: Calcitriol; Cholecalciferol; Dietary Supplements; Humans; Insulin Resistance; Non-alcoholic Fatty Liver Disease; Vitamin D

Type 2 diabetes is clinically associated with progressive necroinflammation and fibrosis in nonalcoholic steatohepatitis (NASH). Advanced glycation end-products (AGEs) accumulate during prolonged hyperglycemia, but the mechanistic pathways that lead to accelerated liver fibrosis have not been well defined. In this study, we show that the AGEs clearance receptor AGER1 was downregulated in patients with NASH and diabetes and in our NASH models, whereas the proinflammatory receptor RAGE was induced. These findings were associated with necroinflammatory, fibrogenic, and pro-oxidant activity via the NADPH oxidase 4. Inhibition of AGEs or RAGE deletion in hepatocytes in vivo reversed these effects. We demonstrate that dysregulation of NRF2 by neddylation of cullin 3 was linked to AGER1 downregulation and that induction of NRF2 using an adeno-associated virus-mediated approach in hepatocytes in vivo reversed AGER1 downregulation, lowered the level of AGEs, and improved proinflammatory and fibrogenic responses in mice on a high AGEs diet. In patients with NASH and diabetes or insulin resistance, low AGER1 levels were associated with hepatocyte ballooning degeneration and ductular reaction. Collectively, prolonged exposure to AGEs in the liver promotes an AGER1/RAGE imbalance and consequent redox, inflammatory, and fibrogenic activity in NASH.

Topics: Animals; Ascorbic Acid; Cholecalciferol; Dehydroepiandrosterone; Diabetes Mellitus, Type 2; Disease Models, Animal; Down-Regulation; Hepatocytes; Liver Cirrhosis; Mice; Mice, Knockout; NF-E2-Related Factor 2; Nicotinic Acids; Non-alcoholic Fatty Liver Disease; Plant Extracts; Receptor for Advanced Glycation End Products

Non-alcoholic steatohepatitis (NASH) is recognized as the most severe form of non-alcoholic fatty liver disease, with likely progression to liver cirrhosis and hepatocellular carcinoma. However, there is no unified standard for diagnosis and therapeutics. This study aimed to characterize lipid transfer/metabolic proteins as non-invasive diagnostic markers, and to evaluate the therapeutic effects of phototherapy on the progression of NASH in rats.. Lewis rats given a choline-deficient and iron-supplemented l-amino acid-defined (CDAA) diet and Zucker fa/fa rats were used as a diet-induced and an obesity-related NASH models, respectively, with or without phototherapy.. Serum apolipoprotein E and low molecular weight-adiponectin levels were gradually reduced and reached the lowest level at fatty liver/NASH stage both in CDAA diet-induced NASH model and in genetically obese model. Total-adiponectin levels were dramatically elevated after NASH was established in CDAA diet-induced NASH model. Phototherapy ameliorated hepatocyte apoptosis, inflammation, fibrosis, and insulin/leptin resistance caused by CDAA diet with alteration of the levels of lipid transfer/metabolic proteins and elevation of the circulating active form of vitamin D(3). Vitamin D(3) supplementation ameliorated NASH progression in CDAA diet-induced NASH model. However, phototherapy failed to ameliorate the obesity and steatosis, suggesting that phototherapy may possess anti-inflammatory/fibrotic activity rather than anti-obesity/steatotic activity.. These results suggest that serum lipid transfer/metabolic proteins and vitamin D(3) status may be effective biomarkers for non-invasive diagnosis of NASH progression, and that phototherapy may be a good complementary therapy for NASH because of its regulation of lipid transfer/metabolic proteins and vitamin D(3).

Topics: Adiponectin; Animals; Apolipoprotein A-I; Apolipoproteins E; Apoproteins; Carrier Proteins; Cholecalciferol; Cytokines; Disease Models, Animal; Disease Progression; Fatty Liver; Gene Expression; Heliotherapy; Liver; Male; Non-alcoholic Fatty Liver Disease; Obesity; Rats; Rats, Inbred Lew; Rats, Zucker; Receptors, Adiponectin