• Clinical and Experimental Pediatrics
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• 제48권2호
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• pp.126-137
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• 2005

New insights in the complex metabolic pathways and its control mechanism for energy homeostasis have refined our understanding of the pathophysiology of obesity. It is now recognized that there are several additional regulatory mechanism such as peripheral signals including leptin, ghrelin, GLP-1 and PYY and cellular signals including uncoupling proteins and ${\beta}$ Adrenergic receptors, which contribute to the regulation of food intake and energy expenditure, respectively. In addition, the function of adipocyte as an endocrine organ in energy homeostasis has been recently emphasized. Recent findings suggest that elevated levels of adipokines, such as leptin, adiponectin, resistin and TNF-${\alpha}$, in addition to increased free fatty acid level could be related to the pathophysiology of insulin resistance in obesity. For effective treatments and prevention of obesity, further studies on the circuits of neural and endocrine interactions in the regulation of energy homeostasis are needed.

• BMB Reports
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• 제57권9호
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• pp.400-416
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• 2024

Matricellular proteins are integral non-structural components of the extracellular matrix. They serve as essential modulators of immunometabolism and tissue homeostasis, playing critical roles in physiological and pathological conditions. These extracellular matrix proteins including thrombospondins, osteopontin, tenascins, the secreted protein acidic and rich in cysteine (SPARC) family, the Cyr61, CTGF, NOV (CCN) family, and fibulins have multi-faceted functions in regulating immune cell functions, metabolic pathways, and tissue homeostasis. They are involved in immune-metabolic regulation and influence processes such as insulin signaling, adipogenesis, lipid metabolism, and immune cell function, playing significant roles in metabolic disorders such as obesity and diabetes. Furthermore, their modulation of tissue homeostasis processes including cellular adhesion, differentiation, migration, repair, and regeneration is instrumental for maintaining tissue integrity and function. The importance of these proteins in maintaining physiological equilibrium is underscored by the fact that alterations in their expression or function often coincide with disease manifestation. This review contributes to our growing understanding of these proteins, their mechanisms, and their potential therapeutic applications.

• Preventive Nutrition and Food Science
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• 제2권1호
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• pp.35-41
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• 1997

The pancreas is an important organ in the maintenance of zinc homeostasis. Endogenous zinc is con-tinuously secreted via pancreatic exocrine fluid or to a lesser extent in bile. Much of the endogenous secretion must be reabsorbed to sustain zinc homeostasis. The objective of this study was to estimate the relative size of the pancreatic/biliary zinc pool in comparision to the dietary zinc intake, and to study the effect of the phytate and calcium on the zinc homeostasis using a rat model. At the termination of the experiment, pan-creatic/biliary fluid was collected from the rats. Both radioactivity and total zinc were measured and the relative size of the pancreatic/biliary zinc pool was estimated. To determine the effect of phytate and calcium on zinc homeostsis, dietary zinc intake, the amount of zinc in pancreatic.biliary fluid and fecal zinc excretion were measured. The flow rate of pancreatic/biliary fluid, as corrected for tubing constriction, gives the corrected zinc concentration in the pancreatic/biliary fluid was 2.2 times higher than dietary zinc intake. To maintain zinc homeostasis, zinc absorption/reabsorption was very efficient in the current model; 76%, 88% of absorption/reabsorption for low calcium group and high calcium group 81% for phytate group and non-phytate group, respectively.

• BMB Reports
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• 제53권4호
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• pp.218-222
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• 2020

Excessive and hyperactive osteoclast activity causes bone diseases such as osteoporosis and periodontitis. Thus, the regulation of osteoclast differentiation has clinical implications. We recently reported that dehydrocostus lactone (DL) inhibits osteoclast differentiation by regulating a nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1), but the underlying mechanism remains to be elucidated. Here we demonstrated that DL inhibits NFATc1 by regulating nuclear factor-κB (NF-κB), activator protein-1 (AP-1), and nuclear factor-erythroid 2-related factor 2 (Nrf2). DL attenuated IκBα phosphorylation and p65 nuclear translocation as well as decreased the expression of NF-κB target genes and c-Fos. It also inhibited c-Jun N-terminal kinase (JNK) but not p38 or extracellular signal-regulated kinase. The reporter assay revealed that DL inhibits NF-κB and AP-1 activation. In addition, DL reduced reactive oxygen species either by scavenging them or by activating Nrf2. The DL inhibition of NFATc1 expression and osteoclast differentiation was less effective in Nrf2-deficient cells. Collectively, these results suggest that DL regulates NFATc1 by inhibiting NF-κB and AP-1 via down-regulation of IκB kinase and JNK as well as by activating Nrf2, and thereby attenuates osteoclast differentiation.

• BMB Reports
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• 제47권9호
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• pp.475-482
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• 2014

Ubiquitin (Ub) is a versatile signaling molecule that plays important roles in a variety of cellular processes. Cellular Ub pools, which are composed of free Ub and Ub conjugates, are in dynamic equilibrium inside cells. In particular, increasing evidence suggests that Ub homeostasis, or the maintenance of free Ub above certain threshold levels, is important for cellular function and survival under normal or stress conditions. Accurate determination of various Ub species, including levels of free Ub and specific Ub chain linkages, have become possible in biological specimens as a result of the introduction of the proteomic approach using mass spectrometry. This technology has facilitated research on dynamic properties of cellular Ub pools and has provided tools for in-depth investigation of Ub homeostasis. In this review, we have also discussed the consequences of the disruption of Ub pool dynamics and homeostasis via deletion of polyubiquitin genes or mutations of deubiquitinating enzymes. The common consequence was a reduced availability of free Ub and a significant impact on the function and viability of cells. These observations further indicate that the levels of free Ub are important determinants for cellular protection.

• BMB Reports
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• 제53권9호
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• pp.472-477
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• 2020

Osteoclasts are hematopoietic-derived cells that resorb bone. They are required to maintain proper bone homeostasis and skeletal strength. Although osteoclast differentiation depends on receptor activator of NF-κB ligand (RANKL) stimulation, additional molecules further contribute to osteoclast maturation. Here, we demonstrate that protocadherin-7 (Pcdh7) regulates formation of multinucleated osteoclasts and contributes to maintenance of bone homeostasis. We found that Pcdh7 expression is induced by RANKL stimulation, and that RNAi-mediated knockdown of Pcdh7 resulted in impaired formation of osteoclasts. We generated Pcdh7-deficient mice and found increased bone mass due to decreased bone resorption but without any defect in bone formation. Using an in vitro culture system, it was revealed that formation of multinucleated osteoclasts is impaired in Pcdh7-deficient cultures, while no apparent defects were observed in differentiation and function of Pcdh7-deficient osteoblasts. Taken together, these results reveal an osteoclast cell-intrinsic role for Pcdh7 in maintaining bone homeostasis.

• Journal of Microbiology and Biotechnology
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• 제31권6호
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• pp.765-774
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• 2021

Although research on the osteal signaling pathway has progressed, understanding of gut microbial-dependent signaling pathways for metabolic and immune bone homeostasis remains elusive. In recent years, the study of gut microbiota has shed light on our understanding of bone homeostasis. Here, we review microbiota-mediated gut-bone crosstalk via bone morphogenetic protein/SMADs, Wnt and OPG/receptor activator of nuclear factor-kappa B ligand signaling pathways in direct (translocation) and indirect (metabolite) manners. The mechanisms underlying gut microbiota involvement in these signaling pathways are relevant in immune responses, secretion of hormones, fate of osteoblasts and osteoclasts and absorption of calcium. Collectively, we propose a signaling network for maintaining a dynamic homeostasis between the skeletal system and the gut ecosystem. Additionally, the role of gut microbial improvement by dietary intervention in osteal signaling pathways has also been elucidated. This review provides unique resources from the gut microbial perspective for the discovery of new strategies for further improving treatment of bone diseases by increasing the abundance of targeted gut microbiota.

• Clinical and Experimental Pediatrics
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• 제49권5호
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• pp.470-474
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• 2006

Hypokalemia and hyperkalemia are the most commonly encountered electrolyte abnormalities in hospitalized patients. Because untreated hypokalemia or hyperkalemia is associated with high morbidity and mortality, it is important to recognize and treat them immediately. Hypokalemia and hyperkalemia can result from disruptions in transcellular homeostasis or in the renal regulation of $K^+$ excretion. Although the recognition is simple, appropriate management requires an understanding of normal $K^+$ homeostasis and pathophysiology. In this article, normal $K^+$ homeostasis, pathophysiology, diagnosis and management of hypokalemia and hypokalemia are discussed.

• 셀메드
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• 제14권4호
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• pp.73.1-73.4
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• 2024

Objective: Case study on improving body homeostasis by ortho-cellular nutrition therapy. Methods: A 48-year-old Korean man underwent OCNT due to symptoms of insomnia and decreased physical function due to extreme chronic stress. Results: After exposure to OCNT, fatigue, sleep quality, and brain fog symptoms improved, and overall physical performance improved, including liver function recovery. Conclusion: For people who suffer from symptoms of decreased physical function in various aspects due to extreme stress, applying OCNT can help alleviate symptoms.

• BMB Reports
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• 제43권9호
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• pp.584-592
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• 2010

Tetrahydrobiopterin (BH4) is a multifunctional cofactor of aromatic amino acid hydroxylases and nitric oxide synthase (NOS) as well as an intracellular antioxidant in animals. Through regulation of NOS activity BH4 plays a pivotal role not only in a variety of normal cellular functions but also in the pathogenesis of cardiovascular and neurodegenerative diseases, which develop under oxidative stress conditions. It appears that a balanced interplay between BH4 and NOS is crucial for cellular fate. If cellular BH4 homeostasis maintained by BH4 synthesis and regeneration fails to cope with increased oxidative stress, NOS is uncoupled to generate superoxide rather than NO and, in turn, exacerbates impaired BH4 homeostasis, thereby leading to cell death. The fundamental biochemical events involved in the BH4-NOS interplay are essentially the same, as revealed in mammalian endothelial, cardiac, and neuronal cells. This review summarizes information on the cellular BH4 homeostasis in mammals, focusing on its regulation under normal and oxidative stress conditions.