• Journal of the Korean Magnetic Resonance Society
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• v.16 no.2
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• pp.147-161
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• 2012

Human melanocortin-4 receptor (hMC4R) among MC-Rs, expressed in the brain, is in charge of the control on energy homeostasis and food intake. The structure and function of human MC4R have been studied to understand their essential function and roles. To investigate the structure and function, it is necessary to prepare sufficient amounts of proteins. However, their expression and purification is demanding and time-consuming due to their innate insoluble and toxic properties. The heterozygous mutations of hMC4R, exchange of Asp 90 to Asn located in second transmembrane, cause severe obesity in human. To obtain purified hMC4R wt-TM2 for structural studies, it was first over-expressed and purified by fast protein liquid chromatography (FPLC) and then solution NMR studies were performed to get high-resolution spectra. In here, we established optimized purification scheme to get more purified target peptide.

• Laboraroty Animal Research
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• v.34 no.4
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• pp.140-146
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• 2018

Though bile acids have been well known as digestive juice, recent studies have demonstrated that bile acids bind to their endogenous receptors, including Farnesoid X receptor (FXR) and G protein-coupled bile acid receptor 1 (GPBAR1; TGR5) and serve as hormone to control various biological processes, including cholesterol/bile acid metabolism, glucose/lipid metabolism, immune responses, and energy metabolism. Deficiency of those bile acid receptors has been reported to induce diverse metabolic syndromes such as obesity, hyperlipidemia, hyperglycemia, and insulin resistance. As consistent, numerous studies have reported alteration of bile acid signaling pathways in type II diabetes patients. Interestingly, bile acids have shown to activate TGR5 in intestinal L cells and enhance secretion of glucagon-like peptide 1 (GLP-1) to potentiate insulin secretion in response to glucose. Moreover, FXR has been shown to crosstalk with TGR5 to control GLP-1 secretion. Altogether, bile acid receptors, FXR and TGR5 are potent therapeutic targets for the treatment of metabolic diseases, including type II diabetes.

• Journal of Veterinary Science
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• v.19 no.6
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• pp.798-807
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• 2018

Several studies have reported the effect of absorption of procyanidins and their contribution to the small intestine. However, differences between dietary interventions of procyanidins and interventions via antibiotic feeding in pigs are rarely reported. Following 16S rRNA gene Illumina MiSeq sequencing, we observed that both procyanidin administration for 2 months (procyanidin-1 group) and continuous antibiotic feeding for 1 month followed by procyanidin for 1 month (procyanidin-2 group) increased the number of operational taxonomic units, as well as the Chao 1 and ACE indices, compared to those in pigs undergoing antibiotic administration for 2 months (antibiotic group). The genera Fibrobacter and Spirochaete were more abundant in the antibiotic group than in the procyanidin-1 and procyanidin-2 groups. Principal component analysis revealed clear separations among the three groups. Additionally, using the online Molecular Ecological Network Analyses pipeline, three co-occurrence networks were constructed; Lactobacillus was in a co-occurrence relationship with Trichococcus and Desulfovibrio and a co-exclusion relationship with Bacillus and Spharerochaeta. Furthermore, metabolic function analysis by phylogenetic investigation of communities by reconstruction of unobserved states demonstrated modulation of pathways involved in the metabolism of carbohydrates, amino acids, energy, and nucleotides. These data suggest that procyanidin influences the gut microbiota and the intestinal metabolic function to produce beneficial effects on metabolic homeostasis.

• BMB Reports
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• v.56 no.11
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• pp.575-583
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• 2023

Mitochondria, fundamental cellular organelles that govern energy metabolism, hold a pivotal role in cellular vitality. While consuming dioxygen to produce adenosine triphosphate (ATP), the electron transfer process within mitochondria can engender the formation of reactive oxygen species that exert dual roles in endothelial homeostatic signaling and oxidative stress. In the context of the intricate electron transfer process, several metal ions that include copper, iron, zinc, and manganese serve as crucial cofactors in mitochondrial metalloenzymes to mediate the synthesis of ATP and antioxidant defense. In this mini review, we provide a comprehensive understanding of the coordination chemistry of mitochondrial cuproenzymes. In detail, cytochrome c oxidase (CcO) reduces dioxygen to water coupled with proton pumping to generate an electrochemical gradient, while superoxide dismutase 1 (SOD1) functions in detoxifying superoxide into hydrogen peroxide. With an emphasis on the catalytic reactions of the copper metalloenzymes and insights into their ligand environment, we also outline the metalation process of these enzymes throughout the copper trafficking system. The impairment of copper homeostasis can trigger mitochondrial dysfunction, and potentially lead to the development of copper-related disorders. We describe the current knowledge regarding copper-mediated toxicity mechanisms, thereby shedding light on prospective therapeutic strategies for pathologies intertwined with copper dyshomeostasis.

• International Journal of Oral Biology
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• v.48 no.4
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• pp.33-44
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• 2023

In this review, the regulatory mechanisms of autophagy were described, and its interaction with apoptosis was identified. The role of autophagy in embryogenesis, tooth development, and cell differentiation were also investigated. Autophagy is regulated by various autophagy-related genes and those related to stress response. Highly active autophagy occurrences have been reported during cell differentiation before implantation after fertilization. Autophagy is involved in energy generation and supplies nutrients during early birth, essential to compensate for their deficient supply from the placenta. The contribution of autophagy during tooth development, such as the shape of the crown and root formation, ivory, and homeostasis in cells, was also observed. Genes control autophagy, and studying the role of autophagy in cell differentiation and development was useful for understanding human aging, illness, and health. In the future, the role of specific mechanisms in the development and differentiation of autophagy may increase the understanding of the pathological mechanisms of disease and development processes and is expected to reduce the treatment of various diseases by modulating the autophagic phenomenon.

• Journal of Animal Science and Technology
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• v.66 no.2
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• pp.425-437
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• 2024

Exercise plays an important role in regulating energy homeostasis, which affects the diversity of the intestinal microbial community in humans and animals. To the best of the authors' knowledge, few studies have reported the associations between horse gut microbiota along with their predicted metabolic activities and the athletic ability of Jeju horses and Thoroughbreds living in Korea. This study was conducted to investigate the association between the gut microbiota and athletic performance in horses. This study sequenced the V3 and V4 hypervariable regions of the partial 16S rRNA genes obtained from racehorse fecal samples and compared the fecal microbiota between high- and low-performance Jeju horses and Thoroughbreds. Forty-nine fecal samples were divided into four groups: high-performance Jeju horses (HJ, n = 13), low-performance Jeju horses (LJ, n = 17), high-performance Thoroughbreds (HT, n = 9), and low-performance Thoroughbreds (LT, n = 10). The high-performance horse groups had a higher diversity of the bacterial community than the low-performance horse groups. Two common functional metabolic activities of the hindgut microbiota (i.e., tryptophan and succinate syntheses) were observed between the low-performance horse groups, indicating dysbiosis of gut microbiota and fatigue from exercise. On the other hand, high-performance horse groups showed enriched production of polyamines, butyrate, and vitamin K. The racing performance may be associated with the composition of the intestinal microbiota of Jeju horses and Thoroughbreds in Korea.

• Molecules and Cells
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• v.46 no.12
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• pp.727-735
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• 2023

Stem cells require high amounts of energy to replicate their genome and organelles and differentiate into numerous cell types. Therefore, metabolic stress has a major impact on stem cell fate determination, including self-renewal, quiescence, and differentiation. Lysosomes are catabolic organelles that influence stem cell function and fate by regulating the degradation of intracellular components and maintaining cellular homeostasis in response to metabolic stress. Lysosomal functions altered by metabolic stress are tightly regulated by the transcription factor EB (TFEB) and TFE3, critical regulators of lysosomal gene expression. Therefore, understanding the regulatory mechanism of TFEB-mediated lysosomal function may provide some insight into stem cell fate determination under metabolic stress. In this review, we summarize the molecular mechanism of TFEB/TFE3 in modulating stem cell lysosomal function and then elucidate the role of TFEB/TFE3-mediated transcriptional activity in the determination of stem cell fate under metabolic stress.

• Journal of Applied Biological Chemistry
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• v.53 no.1
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• pp.44-50
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• 2010

Tae-Um-Jo-wee-Tang (TUJWT) and Do-Dam-Tang (DDT) have been used as an anti-obesity herbal medicine but their effect and mechanism of action have not been studied. We investigated the effects of TUJWT and DDT on energy and glucose homeostasis using Sprague Dawley female rats with diet-induced obesity. The mechanisms of action of TUJWT and DDT were studied whether they had anti-obesity effects. Rats fed a high-fat diet were divided into 3 groups: rats in each group received 2 g water extracts of modified TUJWT and DDT, or 2 g cellulose per kg body weight (a negative control) on a daily basis. A further group was fed a low-fat diet as a positive control. We found that DDT significantly decreased body weight and body fat (mesenteric fat and retroperitoneal fat) more than the control. This decrease was due to the reduction in energy intake but no changes of energy expenditure. However, DDT increased fat oxidation as a major energy source than the control. In addition, modified TUJWT and DDT improved glucose tolerance without changing serum insulin levels during an oral glucose tolerance test. In conclusion, DDT have a better anti-obesity effect than TUJWT by decreasing energy intake in female rats with diet-induced obesity. It also improves glucose tolerance.

• Molecules and Cells
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• v.38 no.10
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• pp.843-850
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• 2015

The1hepatic cell death induced by acetaminophen (APAP) is closely related to cellular adenosine triphosphate (ATP) depletion, which is mainly caused by mitochondrial dysfunction. Adenosine monophosphate (AMP)-activated protein kinase (AMPK) is a key sensor of low energy status. AMPK regulates metabolic homeostasis by stimulating catabolic metabolism and suppressing anabolic pathways to increase cellular energy levels. We found that the decrease in active phosphorylation of AMPK in response to APAP correlates with decreased ATP levels, in vivo. Therefore, we hypothesized that the enhanced production of ATP via AMPK stimulation can lead to amelioration of APAP-induced liver failure. A769662, an allosteric activator of AMPK, produced a strong synergistic effect on AMPK Thr172 phosphorylation with APAP in primary hepatocytes and liver tissue. Interestingly, activation of AMPK by A769662 ameliorated the APAP-induced hepatotoxicity in C57BL/6N mice treated with APAP at a dose of 400 mg/kg intraperitoneally. However, mice treated with APAP alone developed massive centrilobular necrosis, and APAP increased their serum alanine aminotransferase and aspartate aminotransferase levels. Furthermore, A769662 administration prevented the loss of intracellular ATP without interfering with the APAP-mediated reduction of mitochondrial dysfunction. In contrast, inhibition of glycolysis by 2-deoxy-glucose eliminated the beneficial effects of A769662 on APAP-mediated liver injury. In conclusion, A769662 can effectively protect mice against APAP-induced liver injury through ATP synthesis by anaerobic glycolysis. Furthermore, stimulation of AMPK may have potential therapeutic application for APAP overdose.

• Molecules and Cells
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• v.43 no.1
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• pp.58-65
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• 2020

Fat mass and obesity-associated (FTO) gene helps to regulate energy homeostasis in mammals by controlling energy expenditure. In addition, FTO functions in the regulation of obesity and adipogenic differentiation; however, a role in osteogenic differentiation is unknown. This study investigated the effects of FTO on osteogenic differentiation of C3H10T1/2 cells and the underlying mechanism. Expression of osteogenic and endoplasmic reticulum (ER) stress markers were characterized by reverse-transcriptase polymerase chain reaction and western blotting. Alkaline phosphatase (ALP) staining was performed to assess ALP activity. BMP2 treatment increased mRNA expression of osteogenic genes and FTO. Overexpression of FTO increased expression of the osteogenic genes distal-less homeobox5 (Dlx5) and runt-related transcription factor 2 (Runx2). Activation of adenosine monophosphate-activated protein kinase (AMPK) increased FTO expression, and there was a positive feedback loop between FTO and p-AMPK. p-AMPK and FTO induced mild ER stress; however, tunicamycin-induced severe ER stress suppressed FTO expression and AMPK activation. In summary, FTO induces osteogenic differentiation of C3H10T1/2 cells upon BMP2 treatment by inducing mild ER stress via a positive feedback loop with p-AMPK. FTO expression and AMPK activation induce mild ER stress. By contrast, severe ER stress inhibits osteogenic differentiation by suppressing FTO expression and AMPK activation.