• Molecules and Cells
• /
• v.40 no.3
• /
• pp.186-194
• /
• 2017

A brain-enriched secreting signal peptide, NELL2, has been suggested to play multiple roles in the development, survival, and activity of neurons in mammal. We investigated here a possible involvement of central NELL2 in regulating feeding behavior and metabolism. In situ hybridization and an immunohistochemical approach were used to determine expression of NELL2 as well as its colocalization with proopiomelanocortin (POMC) and neuropeptide Y (NPY) in the rat hypothalamus. To investigate the effect of NELL2 on feeding behavior, 2 nmole of antisense NELL2 oligodeoxynucleotide was administered into the lateral ventricle of adult male rat brains for 6 consecutive days, and changes in daily body weight, food, and water intake were monitored. Metabolic state-dependent NELL2 expression in the hypothalamus was tested in vivo using a fasting model. NELL2 was noticeably expressed in the hypothalamic nuclei controlling feeding behavior. Furthermore, all arcuatic POMC and NPY positive neurons produced NELL2. The NELL2 gene expression in the hypothalamus was up-regulated by fasting. However, NELL2 did not affect POMC and NPY gene expression in the hypothalamus. A blockade of NELL2 production in the hypothalamus led to a reduction in daily food intake, followed by a loss in body weight without a change in daily water intake in normal diet condition. NELL2 did not affect short-term hunger dependent appetite behavior. Our data suggests that hypothalamic NELL2 is associated with appetite behavior, and thus central NELL2 could be a new therapeutic target for obesity.

• Nutrition Research and Practice
• /
• v.16 no.1
• /
• pp.46-59
• /
• 2022

BACKGROUND/OBJECTIVES: Aster yomena (Kitam.) Honda (AY) has remarkable bioactivities, such as antioxidant, anti-inflammation, and anti-cancer activities. On the other hand, the effects of AY against obesity-induced insulin resistance have not been reported. Therefore, this study examined the potential of AY against obesity-associated insulin resistance in high-fat diet (HFD)-fed mice. MATERIALS/METHODS: An obesity model was established by feeding C57BL/6J mice a 60% HFD for 16 weeks. The C57BL6/When ethyl acetate fraction from AY (EFAY) at doses of 100 and 200 mg/kg/day was administered orally to mice fed a HFD for the last 4 weeks. Normal and control groups were administered water orally. The body weight and fasting blood glucose were measured every week. Dietary intake was measured every other day. After dissection, blood and tissues were collected from the mice. RESULTS: The administration of EFAY reduced body and organ weights significantly compared to HFD-fed control mice. The EFAY-administered groups also improved the serum lipid profile by decreasing the triglyceride, total cholesterol, and low-density lipoprotein compared to the control group. In addition, EFAY ameliorated the insulin resistance-related metabolic dysfunctions, including the fasting blood glucose and serum insulin level, compared to the HFD-fed control mice. The EFAY inhibited lipid synthesis and insulin resistance by down-regulation of hepatic fatty acid synthase and up-regulation of the AMP-activated protein kinase pathway. EFAY also reduced lipid peroxidation in the liver, indicating that EFAY protected hepatic injury induced by obesity. CONCLUSIONS: These results suggest that EFAY improved obesity-associated insulin resistance by regulating the lipid and glucose metabolism, suggesting that AY could be used as a functional food to prevent obesity and insulin resistance.

• The Journal of the Society of Stroke on Korean Medicine
• /
• v.15 no.1
• /
• pp.1-12
• /
• 2014

■ Objectives This study was designed to investigate the effects of Ephedra Herba hexane fraction on lipid levels in serum and lipid accumulation in liver tissue in Hyperlipidemic mice. ■ Methods Hyperlipidemia was induced by providing high fat diet for 4 weeks. Normal group was provided with normal diet. CTL groupwas provided with high fat diet. Ephedra Herba hexane fraction group was provieded with high fat diet and administered orally in the concentration of 1.5mg/kg body weight/day for 2 weeks. In this experiment, effects on total cholesterol, HDL-cholesterol, triglyceride, AST, ALT, fasting blood glucose in serum were measured. In addition histopathological changes in liver tissue were also observed. ■ Results Ephedra Herba hexane fraction did not affects weight gain, serum AST and ALT in hyperlipidemic mice. Oral administration of Ephedra Herba hexane fraction lowered levels of total cholesterol and triglyceride, which were elevated by induction of hyperlipidemia. In addition, Ephedra Herba hexane fraction group showed downward tendency of lipid accumulation compared with CTL group. Finally, administration of Ephedra Herba hexane fraction lowered fasting blood glucose significantly. And Ephedra Herba hexane fraction also ameliorates anti-oxidative stress systems in internal organs which play key role in disease prevention. ■ Conclusion These results suggest that Ephedra Herba hexane fraction can prevent lipid accumulation in liver tissue through regulation of dyslipidemia and hyperglycaemia.

• Clinical and Experimental Pediatrics
• /
• v.49 no.6
• /
• pp.665-671
• /
• 2006

Purpose : To study the effects of growth hormone(GH) treatment on glucose metabolism and insulin resistance in children with idiopathic short stature(ISS). Methods : Glucose and insulin concentrations were measured during oral glucose tolerance test (OGTT) before and after GH treatment(0.6-0.7 IU/kg/week) in 20 patients with ISS. Insulin resistance was assessed by homeostasis model assessment(HOMA). Results : During OGTT, the mean blood glucose level did not show any significant changes after GH treatment. However, mean blood insulin levels of fasting and 30 minutes of OGTT showed significant increases after GH treatment, accompanying significant increases of insulin resistance. There was no difference in change of glucose, insulin levels and insulin resistance before and after GH treatment between two groups of body mass indices(BMI) of 25< and >25. There also was no significant difference between two groups of with and without family histories of diabetes mellitus (DM). There was no case of newly developed impaired glucose tolerance, fasting glucose tolerance, nor newly developed DM. Conclusion : GH treatment with doses of 0.6-0.7 IU/kg/week for mean 9.6 months in patients with ISS did not show any significant changes in blood glucose levels during OGTT. However, GH treatments induced considerably higher fasting insulin levels compared to pretreatment, resulting in statistically higher insulin resistance. Higher BMI and family history of DM did not induce any significant changes in glucose, insulin level and insulin resistance after GH treatment than the other groups.

• Journal of the Korea Academia-Industrial cooperation Society
• /
• v.19 no.10
• /
• pp.243-253
• /
• 2018

This study aimed to investigate the effects of DCI on glucose control, quality of life(SF-36 Version 2.0, Korean) and SDSCA(Summary of Diabetes Self-Care Activities) in patients with type 2 diabetes mellitus. A randomized, double-blind, placebo-controlled study was performed on 46 patients with HbA1c 7.0% taking triple anti-diabetic drug regimen who visited the department of Endocrinology and Metabolism in Chungnam National University Hospital between March 2015 and May 2016. As a result, DCI treatment in the intervention group resulted in significantly reduced HbA1c levels $8.75{\pm}0.79%$(baseline), $8.36{\pm}1.03%$(after 12weeks), and $8.65{\pm}0.81%$(after 24weeks). However, patients in the control group did not show any significant change. Interestingly, both DCI treatment group and the control group significantly showed improvements in SDSCA. Participants in the intervention group showed a small yet significant improvement in their only fasting blood glucose test in SDSCA and revealed significant increase in the quantitative levels of quality of life, from $73.05{\pm}16.85$ to $82.74{\pm}10.68$. By using pathway analysis, improvement of SDSCA scores(${\beta}=-0.505$, t=-2.743) was the most influential factor to the fasting blood glucose. The quality of life of patients with type 2 diabetes mellitus was affected by changes of SDSCA scores(${\beta}=0.411$, t=2.024) and fasting c-peptide(${\beta}=-0.445$, t=-2.668) in DCI treatment group. In conclusion, treatment of DCI effectively improved glucose control in patients with type 2 DM(HbA1c level>7.0%) after 12 weeks of treatment, although it had no impact on glucose control after 24 weeks of treatment. Improved glucose control may encourage diabetic patients to conduct self-care activities and improve the quality of life. Based on the present study, we suggest that diabetes self-management, as well as consideration of comprehensive laboratory findings, may be important factor in regulating the quality of life in type 2 DM patients.

• Molecular & Cellular Toxicology
• /
• v.4 no.4
• /
• pp.318-322
• /
• 2008

Obesity is an increasing worldwide health problem that is strongly related to the imbalance of food intake and energy metabolism. It was well-known that several substances in the hypothalamus regulate food intake and energy metabolism. We planned an integrative study to elucidate the mechanism of the development of obesity. Firstly, to find candidate genes with the marvelous effect, the different expression in the hypothalamus between ob/ob and 48-h fasting mice was investigated by using DNA microarray technology. As a result, we found 3 genes [peroxisome proliferator activated receptor, gamma, coactivator 1 alpha (Ppargc1a), calmodulin 1 (Calm1), and complexin 2 (Cplx2)] showing the different hypothalamic expression between ob/ob and 48-h fasting mice. Secondly, a genetic approach on PPARGC1A gene was performed, because PPARGC1A acts as a transcriptional coactivator and a metabolic regulator. Two hundred forty three obese female patients with body mass index (BMI)${\geq}$25 and 285 control female subjects with BMI 18 to<23 were recruited according to the Classification of Korean Society for the Study of Obesity. Among the coding single nucleotide polymorphisms (cSNPs) of PPARGC1A, 2 missense SNPs (rs8192678, Gly482Ser; rs3736265, Thr612Met) and 1 synonymous SNP (rs3755863, Thr528Thr) were selected, and analyzed by PCR-RFLP and pyrosequencing. For the analysis of genetic data, chi-square ($X^2$) test and EH program were used. The rs8192678 was significantly associated with obese women (P<0.0006; odds ratio, 1.5327; 95% confidence interval, 1.2006-1.9568). Haplotypes also showed significant association with obese women ($X^2$=33.28, P<0.0008). These results suggest that PPARGC1A might be related to the development of obesity.

• Nutritional Sciences
• /
• v.7 no.4
• /
• pp.208-213
• /
• 2004

In this study, we examined the effects of dietary 1,3-diacylglycerol (DG) compared to conventional triacylglycerol (TG) oil on the postprandial response of total and chylomicron TG, glucose, insulin, and free fatty acid (FFA). This study was conducted using a cross-over design. Ninety subjects participated in the high-fat meal tolerance test where they were randomly assigned to consume two experimental sandwiches containing mayonnaise with TG or DG oil with a seven-day interval. Blood samples were collected before ingestion and at 2, 3, 4 and 6 hr time point after ingestion and analyzed for total and chylomicron TG, glucose, insulin, FFA and phospholipid fatty acid composition. Both TG and DG ingestion had similar effects on postprandial TG response, but a different response from chylomicron TG. Compared with the TG group, TG levels were significantly lower only at 6 hr time point in the DG group. On the other hand, chylomicron TG rose steeply at 2 hr time point and decreased faster in this group. Also, the adjusted value to fasting levels was the same as the unadjusted level. Fasting levels and net differences in insulin were significantly lower at 3 hr time point where chylomicron TG levels were significantly lower in the DG group. But those of glucose and FFA in the TG and DG groups did not differ significantly. Fasting and postprandial levels of fatty acid composition in serum phospholipids in the two groups did not differ significantly. In conclusion, this study indicated that one could reduce the magnitude of postprandial lipemia without influencing glucose metabolism by consumning DG oil as a substitute for TG oil. Based on the correlation of coronary artery disease and postprandial lipemia, dietary DG ingestion might have a beneficial effect in treating such a disease. Further studies are required to clarify the long-tenn effects of dietary DG on blood lipid levels in humans.

• Asian-Australasian Journal of Animal Sciences
• /
• v.23 no.2
• /
• pp.205-212
• /
• 2010

The effects of chromium (Cr), dietary crude protein (CP) level, and potential interactions of these two factors were investigated in term of energy metabolism in lambs. Forty-eight 9-week-old weaned lambs (Dorper${\times}$Small-tail Han sheep, male, mean initial body weight = 22.96 kg${\pm}$2.60 kg) were used in a 2${\times}$3 factorial arrangement of supplemental Cr (0 ${\mu}g$/kg, 400 $\mu{g}$/kg or 800 ${\mu}g$/kg from chromium yeast) and protein levels (low protein: 157 g/d to 171 g/d for each animal, or high protein: 189 g/d to 209 g/d for each animal). Blood samples were collected at the beginning and end of the feeding trial. The lambs were then sacrificed and tissue samples were frozen for further analysis. Chromium at 400 ${\mu}g$/kg decreased fasting insulin level and the ratio of plasma insulin to glucagon, but these differences were not statistically significant; in contrast, chromium at 800 ${\mu}g$/kg increased the ratio significantly (p<0.05). Protein at the high level increased plasma tumor necrosis factor $\alpha$ (TNF-$\alpha$) level (p = 0.060). Liver glycogen content was increased significantly by Cr (p<0.05), which also increased liver glucose-6-phosphatase (G-6-Pase) and adipose hormone-sensitive lipase (HSL) activity. At 400 ${\mu}g$/kg, Cr increased muscle hexokinase (HK) activity. High protein significantly increased G-6-Pase activities in both the liver (p<0.05) and the kidney (p<0.05), but significantly decreased fatty acid synthase (FAS) activity in subcutaneous adipose tissue (p<0.05). For HSL activity in adipose tissue, a Cr${\times}$CP interaction (p<0.05) was observed. Overall, Cr improved energy metabolism, primarily by promoting the glycolytic rate and lipolytic processes, and these regulations were implemented mainly through the modulation by Cr of the insulin signal transduction system. High protein improved gluconeogenesis in both liver and kidney. The interaction of Cr${\times}$CP indicated that 400 $\mu{g}$/kg Cr could reduce energy consumption in situations where energy was being conserved, but could improve energy utilization when metabolic rate was increased.

• Journal of the Korean Society of Food Science and Nutrition
• /
• v.25 no.5
• /
• pp.846-854
• /
• 1996

High dietary fiber(DF) diets lower blood glucose and insulin requirements in diabetics. In this study we evaluated the effects of high dietary fiber(DF) food supplements on glucose metabolism in thirty-four subjects with non-insulin-dependent diabetes mellitus(NIDDM). The subjects were divided into three test groups. Each group's prescribed hospital diets were augmented by one of the three following DF supplements for two weeks: Soybean biscuits containing 5g of total DF-the control group(n=15); Biji biscuits containing 20g of total DF-the high insoluble DF group(n=9); and sea tangle biscuits containing 25g of total DF-the high soluble DF group(n=10). The mean daily DF intake of the subjects during the period were: $19.1\pm4.3g$ for the soybean control group; $32.5\pm4.1g$ for the Bijl group; and $38.1\pm5.5g$ for the sea tangle group. The supplementation of the Biji or sea tangle biscuits singnificantly lowered fasting serum glucose levels(p < 0.05) and resulted in the improvement of glucose tolerance. However, the secretions of insulin, C-peptide, and glucagon and Hb $A_{lc}$ concentration were not affected by the high fiber supplementary feeding for two weeks. The urinary excretion of glucose decreased remarkably after the addition of the DF supplements in all three groups(p<0.05). The results indicate that the supplementation of Biji or sea tangle bascuits possesses a beneficial effect on the improvement of glucose metabolism in subjects with NIDDM.

• Nutritional Sciences
• /
• v.6 no.4
• /
• pp.195-200
• /
• 2003

In recent years, the prevalence of type 2 diabetes mellitus has dramatically increased in Korea as the diet has rapidly become westernized. We determined the effect of long-term cola intakes on glucose metabolism and oxidative stress in weanling male Sprague Dawley rats consuming a moderate fat diet Thirty male rats, born from 6 female rats, were randomized into cola or water drinking groups. For 28 weeks, all rats were provided with an ad lib solid diet having 33 percent of its metabolisable energy as fat In addition, rats of the cola group were provided with ad lib cola instead of water. The daily total caloric intake did not differ between groups. The rats in the cola group consumed a higher proportion of carbohydrates, and their mean body weight and fasting serum insulin level were lower than that of the control group. Whole-body glucose disposal rates measured by an euglycemic hyperinsulinemic clamp were higher in the cola group. However, lipid peroxide levels in kidney tissue were higher in the cola group than in the control group. Superoxide dismutase activity in kidney tissues was lower in the cola group compared to the control group, while glutathion peroxidase and catalase activities were not significantly different between the two groups. In conclusion, long-term cola intakes decreased insulin resistance, but increased oxidative stress in kidney tissue due to decreased SOD activities, which may lead to kidney damage. Thus, moderate changes in insulin resistance may not affect the status of oxidative stress, and vice versa.