• IMMUNE NETWORK
• /
• v.16 no.3
• /
• pp.147-158
• /
• 2016

The liver lies at the intersection of multiple metabolic pathways and consequently plays a central role in lipid metabolism. Pathological disturbances in hepatic lipid metabolism are characteristic of chronic metabolic diseases, such as obesity-mediated insulin resistance, which can result in nonalcoholic fatty liver disease (NAFLD). Tissue damage induced in NAFLD activates and recruits liver-resident and non-resident immune cells, resulting in nonalcoholic steatohepatitis (NASH). Importantly, NASH is associated with an increased risk of significant clinical sequelae such as cirrhosis, cardiovascular diseases, and malignancies. In this review, we describe the immunopathogenesis of NASH by defining the known functions of immune cells in the progression and resolution of disease.

• Clinical Nutrition Research
• /
• v.12 no.3
• /
• pp.229-243
• /
• 2023

The rising prevalence of obesity and diabetes is a significant health concern both in globally and is now regarded as a worldwide epidemic. Added sugars like sucrose and high-fructose corn syrup (HFCS) are a major concern due to their link with an increased incidence of diet-induced obesity and diabetes. The purpose of this review is to provide insight into the effects of natural sweeteners as alternatives to sucrose and HFCS, which are known to have negative impacts on metabolic diseases and to promote further research on sugar consumption with a focus on improving metabolic health. The collective evidences suggest that natural alternative sweeteners have positive impacts on various markers associated with obesity and diabetes, including body weight gain, hepatic fat accumulation, abnormal blood glucose or lipid homeostasis, and insulin resistance. Taken together, natural alternative sweeteners can be useful substitutes to decrease the risk of obesity and diabetes compared with sucrose and HFCS.

• Journal of Animal Science and Technology
• /
• v.59 no.1
• /
• pp.1.1-1.11
• /
• 2017

Background: Intrauterine environment plays a pivotal role in the origin of fatal diseases such as the metabolic syndrome. Diabetes is associated with low-grade inflammatory state and dysregulated adipokines production. The aim of this study is to investigate the effect of maternal diabetes on adipocytokines (adiponectin, leptin and TNF-${\alpha}$) production in F1 offspring in rats. Methods: The offspring groups were as follows: F1 offspring of control mothers under control diet (CD) (CF1-CD), F1 offspring of control mothers under high caloric diet (HCD) (CF1-HCD), F1 offspring of diabetic mothers under CD (DF1-CD), and F1 offspring of diabetic mothers under HCD (DF1-HCD). Every 5 weeks post-natal, 10 pups of each subgroup were culled to obtain blood samples for biochemical analysis. Results: The results indicate that DF1-CD and DF1-HCD groups exhibited hyperinsulinemia, dyslipidemia, insulin resistance and impaired glucose homeostasis compared to CF1-CD (p > 0.05). DF1-CD and DF1-HCD groups had high hepatic and muscular depositions of TGs. The significant elevated NEFA level only appeared in offspring of diabetic mothers that was fed HCD. DF1-CD and DF1-HCD groups demonstrated low serum levels of adiponectin, high levels of leptin, and elevated levels of TNF-${\alpha}$ compared to CF1-CD (p > 0.05). These results reveal the disturbed metabolic lipid profile of offspring of diabetic mothers and could guide further characterization of the mechanisms involved. Conclusion: Dysregulated adipocytokines production could be a possible mechanism for the transgenerational transmittance of diabetes, especially following a postnatal diabetogenic environment. Moreover, the exacerbating effects of postnatal HCD on NEFA in rats might be prone to adipcytokine dysregulation. Furthermore, dysregulation of serum adipokines is a prevalent consequence of maternal diabetes and could guide further investigations to predict the development of metabolic disturbances.

• Journal of Nutrition and Health
• /
• v.56 no.6
• /
• pp.629-640
• /
• 2023

Purpose: Non-alcoholic fatty liver disease (NAFLD) is characterized by the accumulation of fat in the liver which is not a result of excessive alcohol consumption. Its global prevalence was estimated to be approximately 32% in the years 1994-2019. More than half of obese individuals and patients with diabetes are reported to have NAFLD as a comorbidity. This study aimed to investigate the impact of the autumn olive (Elaeagnus umbellata Thunb.) berry on insulin resistance and steatosis in rats fed a high-fructose diet. Methods: Six-week-old Wistar rats were divided into four groups. The control group received a diet consisting of 65% corn starch, while the fructose and experimental groups were fed a diet comprising 65% fructose (FRU) and an FRU diet containing 0.5% (low-dose autumn olive berry group; LAO) or 1.0% (high-dose autumn olive berry group; HAO) ethanol extract of autumn olive berry, respectively, for 10 weeks. Results: The HAO group exhibited significantly lower blood glucose levels compared to the fructose-fed group. Both the LAO and HAO groups showed a substantial reduction in serum insulin levels and insulin resistance when compared to the fructose-fed group. The consumption of LAO and HAO significantly ameliorated dyslipidemia and reduced the levels of triglycerides in the liver compared to the fructose-fed group. Additionally, the consumption of HAO resulted in lower serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities compared to the fructose group. The hepatic expression of the sterol regulatory element-binding protein-1c (SREBP-1c) and carbohydrate-responsive element-binding protein (ChREBP) was significantly reduced in the LAO and HAO groups compared to the fructose group. Conclusion: Autumn olive berries improved steatosis by ameliorating insulin resistance and down-regulating the lipogenesis proteins in rats fed on high fructose diet.

• Journal of Life Science
• /
• v.19 no.6
• /
• pp.804-808
• /
• 2009

The purpose of the this study was to examine the effects of 12 weeks of regular aerobic exercise training on hepatic enzymes in type 2 diabetes mellitus (T2DM) patients. The subjects consisted of 13 middle-aged male type 2 diabetes mellitus (T2DM) patients, all of whom had no other complications. Subjects participated in regular aerobic exercise training for 12 weeks, in which they started to exercise for $20{\sim}60$ min, at $60{\sim}80$% $HR_{max}$ (exercise intensity was increased gradually), per day, $3{\sim}5$ times a weeks. The results after 12 weeks were compared to baseline values. Weight and BMI, %body fat, and fasting glucose significantly decreased, and $_{peak}VO_{2}$, exercise time (ET) significantly increased after 12 weeks of aerobic exercise training. On the other hand, there were no significant differences in hepatic enzymes of Albumin, Total bilirubin, Alkaline phosphatate, AST, and ALT after training compared to baseline values. Conclusively, 12 weeks of aerobic exercise training may result in a decrease of insulin resistance factors (Weight, BMI, % body fat, fasting glucose) and an increase of aerobic capacity, but hepatic enzymes did not significantly decrease in middle age T2DM patients.

• Journal of Life Science
• /
• v.31 no.9
• /
• pp.796-805
• /
• 2021

Hepatic endoplasmic reticulum (ER) stress contributes to the development of steatosis and insulin resistance. The components of unfolded protein response (UPR) regulate lipid metabolism. Recent studies have reported an association between ER stress and aberrant cellular lipid control; moreover, research has confirmed the involvement of sterol regulatory element-binding proteins (SREBPs)-the central regulators of lipid metabolism-in the process. However, the exact role of SREBPs in controlling lipid metabolism during ER stress and its contribution to fatty liver disease remain unknown. Here, we show that SREBP-1c deficiency protects against ER stress-induced hepatic steatosis in mice by regulating UPR, inflammation, and fatty acid oxidation. SREBP-1c directly regulated inositol-requiring kinase 1α (IRE1α) expression and mediated ER stress-induced tumor necrosis factor-α activation, leading to a reduction in expression of peroxisome proliferator-activated receptor γ coactivator 1-α and subsequent impairment of fatty acid oxidation. However, the genetic ablation of SREBP-1c prevented these events, alleviating hepatic inflammation and steatosis. Although the mechanism by which SREBP-1c deficiency prevents ER stress-induced inflammatory signaling remains to be elucidated, alteration of the IRE1α signal in SREBP-1c-depleted Kupffer cells might be involved in the signaling. Overall, the results suggest that SREBP-1c plays a crucial role in the regulation of UPR and inflammation in ER stress-induced hepatic steatosis.

• Clinical and Experimental Pediatrics
• /
• v.48 no.11
• /
• pp.1239-1243
• /
• 2005

Purpose : Iron accumulation interferes with hepatic insulin extraction and affects insulin synthesis and secretion. The purpose of this study is to investigate the correlation between serum ferritin and type 2 diabetes mellitus. Methods : We compared the serum ferritin level among 18 patients in an impaired glucose tolerance (IGT) group, 36 in a type 1 diabetes group, eight in a type 2 diabetes group and 29 in a healthy control group. The correlation between serum ferritin levels and sex, body mass indices(BMI), blood pressure(BP), serum fasting sugar level and serum fasting insulin level were also analyzed. Results : The mean log ferritin were $1.33{\pm}0.32$(healthy control group), $1.63{\pm}0.19$(IGT group) and $1.90{\pm}0.30$(type 2 diabetes group). In the IGT group, log ferritin was higher than in the healthy control group(P=0.001). The log ferritin of the type 2 diabetes group was higher than that of the healthy control group(P=0.001). Comparing log ferritin to other factors, log ferritin had a significant positive correlation with body mass indices(P<0.001), systolic blood pressure(P=0.001), and fasting glucose(P=0.001), fasting insulin(P=0.002). Conclusion : Compared to the normal healthy group, serum ferritin concentrations were significantly higher in the IGT group and the type 2 diabetes group. The elevation of serum ferritin concentration may be a risk factor of type 2 diabetes mellitus.

• Development and Reproduction
• /
• v.21 no.3
• /
• pp.259-267
• /
• 2017

Present study aimed to determine the effect of 'bitter melon', a popularly used fruit in Bangladesh and several other Asian countries, on high-fat-diet-induced type 2 diabetes. To investigate the effect, ethanol extract from bitter melon (BME) as a dietary supplement with mouse chow was used. BME was found to significantly attenuate the high-fat diet (HFD) -induced body weight and total fat mass. BME also effectively reduced the insulin resistance induced by the HFD. Furthermore, dietary supplementation of BME was highly effective in increasing insulin sensitivity and reducing hepatic fat and obesity. These results indicate that BME could be effective in attenuating type 2 diabetes and could therefore be a preventive measure against type 2 diabetes.

• Herbal Formula Science
• /
• v.27 no.3
• /
• pp.223-236
• /
• 2019

Dengropanax morfiferus (D), Broussonitia kazinoki (B), and Cudriania tricuspidata (E), a widely cultivated species in South Korea, has been used as traditional medicine to treat numerous diseases. In this study, we evaluated the antidiabetic effects in a various signaling mechanisms using mixed extract and major component contents were analyzed by HPLC in the combined extracts from Dengropanax morfiferus, Broussonitia kazinoki, and Cudriania tricuspidata (DBCE). DBCE inhibited ${\alpha}$-glucosidase and ${\alpha}$-amylase activation and showed potent antioxidant effects, which are evaluated using DPPH, ABTS, and SOD assay. Cytokines, which are released by inflammatory cells in pancreatic islets, are involved in the pathogenesis of type 1 diabetes mellitus. DBCE showed the protective effects in RINm5F cells against cytokines-induced damage by suppressing inducible nitric oxide (NO) synthase and COX-2 expression and NO production. Insulin resistance is the primary characteristic of type 2 diabetes. Therefore, the regulatory effect of DBCE on glucose uptake and production are investigated in insulin-responsive human HepG2 cells. DBCE stimulated glucose uptake, prevented Glut2 and phosphor-IRS1 downregulation induced by high glucose (HG, 30 mM). Moreover, DBCE pretreatment diminished glucose levels, PEPCK and G6Pase overexpression provoked by HG. These findings suggest that DBCE might be used for diabetes treatment through alpha-glucosidase or alpha-amylase activity regulation, pancreatic beta cell protection, hepatic glucose sensitivity improvement. Cytokines, which are released by inflammatory cells' infiltrations around the pancreatic islets, are involved in the pathogenesis of type 1 diabetes mellitus.

• BMB Reports
• /
• v.54 no.6
• /
• pp.323-328
• /
• 2021

Periodontal diseases have been reported to have a multidirectional association with metabolic disorders. We sought to investigate the correlation between periodontitis and diabetes or fatty liver disease using HFD-fed obese mice inoculated with P. gingivalis. Body weight, alveolar bone loss, serological biochemistry, and glucose level were determined to evaluate the pathophysiology of periodontitis and diabetes. For the evaluation of fatty liver disease, hepatic nonalcoholic steatohepatitis (NASH) was assessed by scoring steatosis, inflammation, hepatocyte ballooning and the crucial signaling pathways involved in liver metabolism were analyzed. The C-reactive protein (CRP) level and NASH score in P. gingivalis-infected obese mice were significantly elevated. Particularly, the extensive lobular inflammation was observed in the liver of obese mice infected with P. gingivalis. Moreover, the expression of metabolic regulatory factors, including peroxisome proliferator-activated receptor γ (Pparγ) and the fatty acid transporter Cd36, was up-regulated in the liver of P. gingivalis-infected obese mice. However, inoculation of P. gingivalis had no significant influence on glucose homeostasis, insulin resistance, and hepatic mTOR/AMPK signaling. In conclusion, our results indicate that P. gingivalis can induce the progression of fatty liver disease in HFD-fed mice through the upregulation of CD36-PPARγ axis.