• Journal of Nutrition and Health
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• v.50 no.3
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• pp.217-224
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• 2017

Purpose: Although it is well known thatmortality and morbidity due to cardiovascular diseases are higher in salt-sensitive subjects than in salt-resistant subjects, their underlying mechanisms related to obesity remain unclear. Here, we focused on salt-sensitive gene variants unrelated to monogenic obesity that interacted with sodium intake in humans. Methods: This review was written based on the modified $3^rd$ step of Khans' systematic review. Instead of the literature, subject genes were based on candidate genes screened from our preliminary Genome-Wide Association Study (GWAS). Finally, literature related to five genes strongly associated with salt sensitivity were analyzed to elucidate the mechanism of obesity. Results: Salt sensitivity is a measure of how blood pressure responds to salt intake, and people are either salt-sensitive or salt-resistant. Otherwise, dietary sodium restriction may not be beneficial for everyone since salt sensitivity may be associated with inherited susceptibility. According to our previous GWAS studies, 10 candidate genes and 11 single nucleotide polymorphisms (SNPs) associated with salt sensitivity were suggested, including angiotensin converting enzyme (ACE), ${\alpha}$-adducin1 (ADD1), angiotensinogen (AGT), cytochrome P450 family 11-subfamily ${\beta}$-2 ($CYP11{\beta}$-2), epithelial sodium channel (ENaC), G-protein b3 subunit (GNB3), G protein-coupled receptor kinases type 4 (GRK4 A142V, GRK4 A486V), $11{\beta}$-hydroxysteroid dehydrogenase type-2 (HSD $11{\beta}$-2), neural precursor cell-expressed developmentally down regulated 4 like (NEDD4L),and solute carrier family 12(sodium/chloride transporters)-member 3 (SLC 12A3). We found that polymorphisms of salt-sensitive genes such as ACE, $CYP11{\beta}$-2, GRK4, SLC12A3, and GNB3 may be positively associated with human obesity. Conclusion: Despite gender, ethnic, and age differences in genetics studies, hypertensive obese children and adults who are carriers of specific salt-sensitive genes are recommended to reduce their sodium intake. We believe that our findings can contribute to the prevention of early-onset of chronic diseases in obese children by facilitating personalized diet-management of obesity from childhood to adulthood.

• Nutrition Research and Practice
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• v.9 no.2
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• pp.137-143
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• 2015

BACKGROUND/OBJECTIVES: Mulberry leaves contain quercetin derivatives, which have the effects of reducing obesity and improving lipid and glucose metabolism in mice with obesity. It is not clear whether or not mulberry leaves can directly affect metabolic disorders, in the presence of obesity, because of the interaction between obesity and metabolic disorders. The aim of the current study was to assess the direct action of quercetin derivatives on metabolic disorders in non-obese conditions in short-term high-fat diet fed mice. MATERIALS/METHODS: C57BL/6N mice were fed a high-fat diet, supplemented with either 0% (control), 1%, or 3% mulberry leaf powder (Mul) or 1% catechin powder for five days. Anthropometric parameters and blood biochemistry were determined, and hepatic gene expression associated with lipid and glucose metabolism was analyzed. RESULTS: Body and white fat weights did not differ among the four groups. Plasma triglycerides, total cholesterol, and free fatty acids in the 1%, 3% Mul and catechin groups did not differ significantly from those of the controls, however, plasma glucose and 8-isoprostane levels were significantly reduced. Liver gene expression of gp91phox, a main component of NADPH oxidase, was significantly down-regulated, and PPAR-${\alpha}$, related to ${\beta}$-oxidation, was significantly up-regulated. FAS and GPAT, involved in lipid metabolism, were significantly down-regulated, and Ehhadh was significantly up-regulated. Glucose-metabolism related genes, L-PK and G6Pase, were significantly down-regulated, while GK was significantly up-regulated in the two Mul groups compared to the control group. CONCLUSIONS: Our results suggest that the Mul quercetin derivatives can directly improve lipid and glucose metabolism by reducing oxidative stress and enhancing ${\beta}$-oxidation. The 1% Mul and 1% catechin groups had similar levels of polyphenol compound intake ($0.4{\times}10^{-5}$ vs $0.4{\times}10^{-5}$ mole/5 days) and exhibited similar effects, but neither showed dose-dependent effects on lipid and glucose metabolism or oxidative stress.

• Journal of Korean Medicine Rehabilitation
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• v.29 no.4
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• pp.15-27
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• 2019

Objectives This study was performed to evaluate anti-obesity effects of Crataegus pinnatifida (CP) on high-fat-diet induced obese mice. Methods The experimental animals were divided into four groups: normal diet (NOR) group, high fat diet (HFD) group, HFD+Xenical (XEN) group, and HFD+CP (CP) group. NOR group was fed a normal diet and the other three groups were fed high fat diet during the experiment. After the first two weeks of diet, XEN group and CP group were administered with XEN or CP for seven weeks, respectively. After that, we measured body weight, liver weight, fat weight, food intake, and serum concentrations of lipids and liver enzymes. Also the liver, intestine, fat tissue was removed to estimate the obesity-related mRNA expressions and the stool sample was collected to analyze the gut microbiota. Results We found that body weight, fat weight, and triglyceride level were decreased significantly in CP group compared to HFD group. Also CP significantly suppressed gene expressions associated with lipogenesis and inflammation, and increased gene expressions of browning of white adipose tissue and mitochondrial biogenesis. Moreover, it shifted the microbial diversity closer to that of NOR group and increased Firmicutes/Bacteriodetes ratio. Conclusions These results suggest that CP decrease body weight, fat weight and serum triglyceride. Also it inhibit inflammation and adipogenesis, altering gut microbial diversity and abundance. In conclusion, CP could be used as a therapeutic drug for obesity via gut microbiota modulation.

• Journal of mucopolysaccharidosis and rare diseases
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• v.2 no.2
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• pp.38-40
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• 2016

Prader-Willi syndrome (PWS) is a rare genetic disorder often caused by a deletion of the chromosome 15q11-q13 region inherited from the father or by maternal disomy 15. Growth hormone deficiency with short stature, hypogonadism, cognitive and behavioral problems, analgesia, decreased gastric motility and decreased ability to vomit with hyperphagia are common in PWS leading to severe obesity in early childhood, if not controlled. The goal of this study is to investigate the effects of recombinant human GH (rhGH, henceforth designated GH) on the gene expression related to cognitive function in the brain of PWS mouse model (Snord116del). GH restored the mRNA expression level of several genes in the cerebellum. These data suggest the effect of GH on the expression of cognitive function related genes in cerebellum may provide a mechanism for the GH-induced brain function in PWS patients.

• YAKHAK HOEJI
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• v.56 no.6
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• pp.364-365
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• 2012

Liver is the major organ to regulate the systemic glucose homeostasis and insulin resistance. Excess energy intake leads to triglyceride accumulation in adipose tissue first and subsequent accumulation in liver, resulting in obesity and type 2 diabetes. The representative pathological animal model for obesity associated insulin resistance is a high fat diet (HFD) fed mice model. Given the essential role of liver fat accumulation in developing systemic insulin resistance in obesity, I measured the liver triglyceride contents in HFD fed mice as a function of time. As such, in this report, I show the cause and effect relationship with regard to time during a HFD feeding between a variety of factors that are related to systemic insulin resistance including glucose intolerance, plasma insulin level and inflammatory gene expression in liver and adipose tissue.

• Journal of Physiology & Pathology in Korean Medicine
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• v.26 no.4
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• pp.497-505
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• 2012

To determine the effects of Banggihwanggi-tang(BGHGT) on obesity, the obesity-related factors[gastrin, calcitonin gene related peptide(CGRP), serotonin, ghrelin, obestatin, glucagon-like peptide-1(GLP-1), insulin, orexin, leptin] were investigated in the stomach, pancreas, brain of mice by immunohistochemical(IHC) methods for 4 weeks. The change of body weight was more reduced in BGHGT administered group than that of control group. The IHC density of the gastrin and CGRP positive cells on pylorus was higher in BGHGT administered group than that of control group. The number of ghrelin immunoreactive cells on stomach was lower in BGHGT administered group than that of control group. The IHC of GLP-1 positive cells did not observe in the stomach of BGHGT administered groups. The IHC density of GLP-1 in the pancreas was lower in BGHGT administered group than that of control group. The IHC density of insulin positive cells in the pancreas was lower in BGHGT administered group than that of control group. The IHC density of orexin positive neurons in the diencephalon was slightly higher in BGHGT administered group than that of control group. The IHC density of NPY and leptin positive neurons was slightly higher in BGHGT administered group than that of control group. The IHC density of serotonin positive neurons was higher in BGHGT administered group than that of control group. Therefore, we conclude that BGHGT activates appetite inhibitor through appetite related enteroendocrine cells and neuropeptides in stomach, pancreas and brain, and this activation may also be responsible for the inhibition of feeding behavior.

• Journal of Nutrition and Health
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• v.38 no.8
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• pp.649-655
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• 2005

Nutrigenomics refers to research that investigates the interaction between nutrition and the human genome. Caffeine in tea and coffee is widely and routinely consumed by people. This study was performed to confirm the effect of caffeine treatment on the gene expression and cytokine profiling in 3T3-L1 adipocyte cells using microarray and protein array methodology. Treatment of caffeine in 3T3-L1 adipocyte cells increased expression of several genes related with obesity including adipocyte C1Q and collagen domain containing (ACDC), Adipsin (ADN), uncoupling protein 3(UCP3), while glyceraldehyde-3-phosphate dehydrogenase (GAPDH), which is known as lipid storage enzyme, was decreased by caffeine treatment. Furthermore, cytokines, such as interleukin-3 (IL-3), interleukin-12(IL-12), interleukin-13 (IL-13), granulocyte colony stimulating factor (GCSF), granulocyte macrophage colony stimulating factor (GM-CSF) and vascular endothelial growth factor (VEGF), were decreased in caffeine treated 3T3-L1 adipocyte cells. These results provided interesting information about the genes related with caffeine and cytokine expression profiling in obesity.

• Biomedical Science Letters
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• v.24 no.4
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• pp.311-318
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• 2018

Vitamin C (ascorbic acid) supplementation has been suggested to negatively correlate with obesity in humans and other animals. Previous studies, including ours, have demonstrated that a high-fat diet (HFD) induces obesity and related diseases such as hyperlipidemia, hyperglycemia, insulin resistance, and nonalcoholic fatty liver disease. Here, we investigated the effects of vitamin C on visceral adipocyte hypertrophy and glucose intolerance in C57BL/6J mice. Mice received a low-fat diet (LFD, 10% kcal fat), HFD (45% kcal fat), or the same HFD supplemented with vitamin C (HFD-VC, 1% w/w) for 15 weeks. Visceral adiposity and glucose intolerance were examined using metabolic measurements, histology, and gene expression analyses. Mice in the HFD-VC supplementation group had reduced body weight, mesenteric fat mass, and mesenteric adipocyte size compared with HFD-fed mice. Vitamin C intake in obese mice also decreased the mRNA levels of lipogenesis-related genes (i.e., stearoyl-CoA desaturase 1 and sterol regulatory element-binding protein 1c) in mesenteric adipose tissues, inhibited hyperglycemia, and improved glucose tolerance. In addition, vitamin C attenuated the HFD-induced increase in the size of pancreatic islets. These results suggest that vitamin C suppresses HFD-induced visceral adipocyte hypertrophy and glucose intolerance in part by decreasing the visceral adipose expression of genes involved in lipogenesis.

• Nutrition Research and Practice
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• v.5 no.6
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• pp.511-519
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• 2011

Dietary intake of whole grains reduces the incidence of chronic diseases such as obesity, diabetes, cardiovascular disease, and cancer. In an earlier study, we showed that Panicum miliaceum L. extract (PME) exhibited the highest anti-lipogenic activity in 3T3-L1 cells among extracts of nine different cereal grains tested. In this study, we hypothesized that PME in the diet would lead to weight loss and augmentation of hyperlipidemia by regulating fatty acid metabolism. PME was fed to ob/ob mice at 0%, 0.5%, or 1% (w/w) for 4 weeks. After the experimental period, body weight changes, blood serum and lipid profiles, hepatic fatty acid metabolism-related gene expression, and white adipose tissue (WAT) fatty acid composition were determined. We found that the 1% PME diet, but not the 0.5%, effectively decreased body weight, liver weight, and blood triglyceride and total cholesterol levels (P < 0.05) compared to obese ob/ob mice on a normal diet. Hepatic lipogenic-related gene ($PPAR{\alpha}$, L-FABP, FAS, and SCD1) expression decreased, whereas lipolysis-related gene (CPT1) expression increased in animals fed the 1% PME diet (P < 0.05). Long chain fatty acid content and the ratio of C18:1/C18:0 fatty acids decreased significantly in adipose tissue of animals fed the 1% PME diet (P < 0.05). Serum inflammatory mediators also decreased significantly in animals fed the 1% PME diet compared to those of the ob/ob control group (P < 0.05). These results suggest that PME is useful in the chemoprevention or treatment of obesity and obesity-related disorders.

• Nutrition Research and Practice
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• v.10 no.1
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• pp.115-124
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• 2016

BACKGROUND/OBJECTIVES: This is the first study to identify common genetic factors associated with the basal metabolic rate (BMR) and body mass index (BMI) in obese Korean women including overweight. This will be a basic study for future research of obese gene-BMR interaction. SUBJECTS/METHODS: The experimental design was 2 by 2 with variables of BMR and BMI. A genome-wide association study (GWAS) of single nucleotide polymorphisms (SNPs) was conducted in the overweight and obesity (BMI > $23kg/m^2$) compared to the normality, and in women with low BMR (< 1426.3 kcal/day) compared to high BMR. A total of 140 SNPs reached formal genome-wide statistical significance in this study (P < $1{\times}10^{-4}$). Surveys to estimate energy intake using 24-h recall method for three days and questionnaires for family history, a medical examination, and physical activities were conducted. RESULTS: We found that two NRG3 gene SNPs in the 10q23.1 chromosomal region were highly associated with BMR (rs10786764; $P=8.0{\times}10^{-7}$, rs1040675; $2.3{\times}10^{-6}$) and BMI (rs10786764; $P=2.5{\times}10^{-5}$, rs10786764; $6.57{\times}10^{-5}$). The other genes related to BMI (HSD52, TMA16, MARCH1, NRG1, NRXN3, and STK4) yielded P < $10{\times}10^{-4}$. Five new loci associated with BMR and BMI, including NRG3, OR8U8, BCL2L2-PABPN1, PABPN1, and SLC22A17 were identified in obese Korean women (P < $1{\times}10^{-4}$). In the questionnaire investigation, significant differences were found in the number of starvation periods per week, family history of stomach cancer, coffee intake, and trial of weight control in each group. CONCLUSION: We discovered several common BMR- and BMI-related genes using GWAS. Although most of these newly established loci were not previously associated with obesity, they may provide new insights into body weight regulation. Our findings of five common genes associated with BMR and BMI in Koreans will serve as a reference for replication and validation of future studies on the metabolic rate.