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Leaves of Cudrania tricuspidata on the Shoot Positional Sequence Show Different Inhibition of Adipogenesis Activity in 3T3-L1 Cells (꾸지뽕 신초 엽위별 잎 추출물의 항비만 효과)

  • Park, Ju Ha;Guo, Lu;Kang, He Mi;Son, Beung Gu;Kang, Jum Soon;Lee, Yong Jae;Park, Young Hoon;Je, Byoung Il;Choi, Young Whan
    • Journal of Life Science
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    • v.31 no.2
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    • pp.209-218
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    • 2021
  • This study aimed to evaluate the anti-obesity effects of Cudrania tricuspidata leaf extract in the order of leaf development on the shoot (L0, L1, L2, L3, L4, and L5). The leaves at the apex of a Cudrania tricuspidata shoot were classified as L0; the next leaves of the apex were classified as L1, L2, L3, and L4 from highest to lowest; and the lowest leaf was classified as L5. A series of 70% ethyl alcohol leaf extracts were screened for the inhibitory effects of adipogenesis in 3T3-L1 preadipocytes. We found that the apical leaf extract of Cudrania tricuspidata (CTL0) was the most effective. Next, a study was conducted on the inhibitory action mechanism of CTL0. Treatment with CTL0 significantly suppressed the differentiation of 3T3-L1 preadipocytes in a dose-dependent manner, as confirmed by the decrease in lipid droplet content observed with Oil Red O staining. Treatment with 12.5 ㎍/ml, 25 ㎍/ml, and 50 ㎍/ml of CTL0 significantly reduced the lipid droplet content. Glucose and cellular triglyceride concentrations were reduced in the 3T3-L1 cells on the CTL0-treated medium compared to the differentiation medium (DM control, DMEM + insulin + dexamethasone + rosiglitazone). Compared with DM, CTL0 significantly inhibited the expression of key pro-adipogenic transcription factors, including peroxisome proliferator-activated receptor γ (PPARγ), LPL, A-FABP, and Glut4. These findings show that CTL0 extract has potent anti-obesity effects.

Effect of Acutely Increased Glucose Uptake on Insulin Sensitivity in Rats (단기간의 당섭취 증가가 인슐린 감수성에 미치는 영향)

  • Kim, Yong-Woon;Ma, In-Youl;Lee, Suck-Kang
    • Journal of Yeungnam Medical Science
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    • v.14 no.1
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    • pp.53-66
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    • 1997
  • Insulin resistance is a prominent feature of diabetic state and has heterogeneous nature. However, the pathogenetic sequence of events leading to the emergence of the defect in insulin action remains controversial. It is well-known that prolonged hyperglycemia and hyperinsulinemia are one of the causes of development of insulin resistance, but both hyperglycemia and hyperinsulinemia stimulate glucose uptake in peripheral tissue. Therefore, it is hypothesized that insulin resistance may be generated by a kind of protective mechanism preventing cellular hypertrophy. In this study, to evaluate whether the acutely increased glucose uptake inhibits further glucose transport stimulated by insulin, insulin sensitivity was measured after preloaded glucose infusion for 2 hours at various conditions in rats. And also, to evaluate the mechanism of decreased insulin sensitivity, insulin receptor binding affinity and glucose transporter 4 (GLUT4) protein of plasma membrane of gastrocnemius muscle were assayed after hyperinsulinemic euglycemic clamp studies. Experimental animals were divided into five groups according to conditions of preloaded glucose infusion: group I, basal insulin ($14{\pm}1.9{\mu}U/ml$) and basal glucose ($75{\pm}0.7mg/dl$), by normal saline infusion; group II, normal insulin ($33{\pm}3.8{\mu}U/ml$) and hyperglycemia ($207{\pm}6.3mg/dl$), by somatostatin and glucose infusion; group III, hyperinsulinemia ($134{\pm}34.8{\mu}U/ml$) and hyperglycemia ($204{\pm}4.6mg/dl$), by glucose infusion; group IV, supramaximal insulin ($5006{\pm}396.1{\mu}U/ml$) and euglycemia ($l00{\pm}2.2mg/dl$), by insulin and glucose infusion; group V, supramaximal insulin ($4813{\pm}687.9{\mu}U/ml$) and hyperglycemia ($233{\pm}3.1mg/dl$), by insulin and glucose infusion. Insulin sensitivity was assessed with hyperinsulinemic euglycemic clamp technique. The amounts of preloaded glucose infusion(gm/kg) were $1.88{\pm}0.151$ in group II, $2.69{\pm}0.239$ in group III, $3.54{\pm}0.198$ in group IV, and $4.32{\pm}0.621$ in group V. Disappearance rates of glucose (Rd, mg/kg/min) at steady state of hyperinsulinemic euglycemic clamp studies were $16.9{\pm}3.88$ in group I, $13.5{\pm}1.05$ in group II, $11.2{\pm}1.17$ in group III, $13.2{\pm}2.05$ in group IV, and $10.4{\pm}1.01$ in group V. A negative correlation was observed between amount of preloaded glucose and Rd (r=-0.701, p<0.001) when all studies were combined. Insulin receptor binding affinity and content of GLUT4 were not significantly different in all experimental groups. These results suggest that increased glucose uptake may inhibit further glucose transport and lead to decreased insulin sensitivity.

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Effects of Fattening Period on Growth Performance, Carcass Characteristics and Lipogenic Gene Expression in Hanwoo Steers

  • Kwon, Eung Gi;Park, Byung Ki;Kim, Hyeong Cheol;Cho, Young Moo;Kim, Tae Il;Chang, Sun Sik;Oh, Young Kyoon;Kim, Nam Kuk;Kim, Jun Ho;Kim, Young Jun;Kim, Eun-Jib;Im, Seok Ki;Choi, Nag-Jin
    • Asian-Australasian Journal of Animal Sciences
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    • v.22 no.12
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    • pp.1654-1660
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    • 2009
  • This study was conducted to investigate the effects of different fattening periods i.e. 25, 27 and 29 months of age (25 mo, 27 mo and 29 mo), on feed consumption, body weight gain, carcass parameters, and lipogenic gene expression in 45 Korean native steers (Hanwoo). Daily DM intake was higher in steers on 29 mo compared with those on 25 mo or 27 mo. Daily body weight gain was higher in steers on 25 mo compared with those on 27 mo or 29 mo during fattening and overall experimental periods. Therefore, feed conversion ratio was lower in 25 mo compared with 27 mo or 29 mo during the fattening and whole experimental periods. As expected, slaughter and carcass weights were higher in the order of 29 mo>27 mo>25 mo. Carcass yield grade was relatively lower in 29 mo reflecting higher back fat thickness compared with other treatments, while carcass quality grade was not largely influenced by the treatments. By investigation with an ultra-sound scanning technique, the marbling score was significantly and numerically higher in 25 mo compared with 27 mo or 29 mo. The mRNA levels of stearoyl-CoA desaturase (SCD) gene were gradually increased in the late fattening stages (p<0.01) and mRNA of acetyl-CoA carboxylase (ACC), ATP citrate lyase (ACL) and glucose transporter 4 (GLUT4) gene were highly expressed in 29 mo compared with 25 mo and 27 mo (p<0.05). However, gene expressions of adipocyte fatty acid binding protein 4 (FABP4) and lipoprotein lipase (LPL) were not significantly different among the treatments. Thus the present results indicated that different fattening period has no major effect on carcass characteristics, although 25 mo had a lower carcass weight compared with 27 mo or 29 mo.

In Vitro Development of Somatic Cell Nuclear Transfer Embryo Treated with Flavonoid and Production of Cloned Jeju Black Cattle (플라보노이드 처리된 체세포 핵이식 배아의 체외 발달 및 제주흑우 복제 소 생산)

  • Kim, Eun-Young;Kim, Yeon-Ok;Kim, Jae-Youn;Park, Min-Jee;Park, Hyo-Young;Han, Young-Joon;Mun, Seong-Ho;Oh, Chang-Eon;Kim, Young-Hoon;Lee, Sung-Soo;Ko, Moon-Suck;Park, Se-Pill
    • Reproductive and Developmental Biology
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    • v.34 no.3
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    • pp.127-134
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    • 2010
  • This study was to investigate the effect of flavonoid treatment on in vitro development of bovine somatic cell nuclear transfer (SCNT) embryos, and their pregnancy and delivery rate after embryo transfer into recipient. In experiment 1, to optimize the flavonoid concentration, parthenogenetic day 2 ($\geq$ 2-cell) embryos were cultured in 0 (control), 1, 10 and $20\;{\mu}M$ flavonoid for 6 days. In the results, in vitro development rate was the highest in $10\;{\mu}M$ flavonoid group (57.1%) among treatment groups (control, 49.5%; $1\;{\mu}M$, 54.2%; $20\;{\mu}M$, 37.5%), and numbers of total and ICM cells were significantly (p<0.05) higher in $10\;{\mu}M$ flavonoid group than other groups. We found that $10\;{\mu}M$ flavonoid treatment can significantly (p<0.05) decrease the apoptotic index and derive high expression of anti-oxidant, anti-apoptotic, cell growth and development marker genes such as Mn-SOD, Survivin, Bax inhibitor, Glut-5, In-tau, compared to control group. In experiment 2, to produce the cloned Jeju Black Cattle, beef quality index grade 1 bull somatic cells were transferred into enucleated bovine MII oocytes and reconstructed embryos were cultured in $10\;{\mu}M$ flavonoid added medium. When the in vitro produced day 7 or 8 SCNT blastocysts were transferred into a number of recipients, $10\;{\mu}M$ flavonoid treatment group presented higher pregnancy rate (10.2%, 6/59) than control group (5.9%, 2/34). Total three cloned Jeju Black calves were born. Also, two cloned calves in $10\;{\mu}M$ flavonoid group were born and both were all healthy at present, while the one cloned calf born in control group was dead one month after birth. In addition, when the result of short tandem repeat marker analysis of each cloned calf was investigated, microsatellite loci of 11 numbers matched genotype between donor cell and cloned calf tissue. These results demonstrated that the flavonoid addition in culture medium may have beneficial effects on in vitro and in vivo developmental capacity of SCNT embryos and pregnancy rate.

Anti-diabetic effect of purple corn extract on C57BL/KsJ db/db mice

  • Huang, Bo;Wang, Zhiqiang;Park, Jong Hyuk;Ryu, Ok Hyun;Choi, Moon Ki;Lee, Jae-Yong;Kang, Young-Hee;Lim, Soon Sung
    • Nutrition Research and Practice
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    • v.9 no.1
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    • pp.22-29
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    • 2015
  • BACKGROUND/OBJECTIVES: Recently, anthocyanins have been reported to have various biological activities. Furthermore, anthocyanin-rich purple corn extract (PCE) ameliorated insulin resistance and reduced diabetes-associated mesanginal fibrosis and inflammation, suggesting that it may have benefits for the prevention of diabetes and diabetes complications. In this study, we determined the anthocyanins and non-anthocyanin component of PCE by HPLC-ESI-MS and investigated its anti-diabetic activity and mechanisms using C57BL/KsJ db/db mice. MATERIALS/METHODS: The db/db mice were divided into four groups: diabetic control group (DC), 10 or 50 mg/kg PCE (PCE 10 or PCE 50), or 10 mg/kg pinitol (pinitol 10) and treated with drugs once per day for 8 weeks. During the experiment, body weight and blood glucose levels were measured every week. At the end of treatment, we measured several diabetic parameters. RESULTS: Compared to the DC group, Fasting blood glucose levels were 68% lower in PCE 50 group and 51% lower in the pinitol 10 group. Furthermore, the PCE 50 group showed 2-fold increased C-peptide and adiponectin levels and 20% decreased HbA1c levels, than in the DC group. In pancreatic islets morphology, the PCE- or pinitol-treated mice showed significant prevention of pancreatic ${\beta}$-cell damage and higher insulin content. Microarray analyses results indicating that gene and protein expressions associated with glycolysis and fatty acid metabolism in liver and fat tissues. In addition, purple corn extract increased the phosphorylation of AMP-activated protein kinase (AMPK) and decreased phosphoenolpyruvate carboxykinase (PEPCK), glucose 6-phosphatase (G6pase) genes in liver, and also increased glucose transporter 4 (GLUT4) expressions in skeletal muscle. CONCLUSIONS: Our results suggested that PCE exerted anti-diabetic effects through protection of pancreatic ${\beta}$-cells, increase of insulin secretion and AMPK activation in the liver of C57BL/KsJ db/db mice.

The Role and Regulation of MCL-1 Proteins in Apoptosis Pathway

  • Bae, Jeehyeon
    • Proceedings of the Korean Society of Applied Pharmacology
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    • 2002.07a
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    • pp.113-113
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    • 2002
  • Phylogenetically conserved Bcl-2 family proteins play a pivotal role in the regulation of apoptosis from virus to human. Members of the Bcl-2 family consist of antiapoptotic proteins such as Bcl-2, Bcl-xL, and Bcl-w, and proapoptotic proteins such as BAD, Bax, BOD, and Bok. It has been proposed that anti- and proapoptotic Bcl-2 proteins regulate cell death by binding to each other and forming heterodimers. A delicate balance between anti- and proapoptotic Bcl-2 family members exists in each cell and the relative concentration of these two groups of proteins determines whether the cell survives or undergoes apoptosis. Mcl-1 (Myeloid cell :leukemia-1) is a member of the Bcl-2 family proteins and was originally cloned as a differentiation-induced early gene that was activated in the human myeloblastic leukemia cell line, ML-1 . Mcl-1 is expressed in a wide variety of tissues and cells including neoplastic ones. We recently identified a short splicing variant of Mcl-1 short (Mcl-IS) and designated the known Mcl-1 as Mcl-1 long (Mcl-lL). Mcl-lL protein exhibits antiapoptotic activity and possesses the BH (Bcl-2 homology) 1, BH2, BH3, and transmembrane (TM) domains found in related Bcl-2 proteins. In contrast, Mcl-1 S is a BH3 domain-only proapoptotic protein that heterodimerizes with Mcl-lL. Although both Mc1-lL and Mcl-lS proteins contain BH domains fecund in other Bcl-2 family proteins, they are distinguished by their unusually long N-terminal sequences containing PEST (proline, glutamic acid, serine, and threonine) motifs, four pairs of arginine residues, and alanine- and glycine-rich regions. In addition, the expression pattern of Mcl-1 protein is different from that of Bcl-2 suggesting a unique role (or Mcl-1 in apoptosis regulation. Tankyrasel (TRF1-interacting, ankyrin-related ADP-related polymerasel) was originally isolated based on its binding to TRF 1 (telomeric repeat binding factor-1) and contains the sterile alpha motif (SAM) module, 24 ankyrin (ANK) repeats, and the catalytic domain of poly(adenosine diphosphate-ribose) polymerase (PARP). Previous studies showed that tankyrasel promotes telomere elongation in human cells presumably by inhibiting TRFI though its poly(ADP-ribosyl)action by tankyrasel . In addition, tankyrasel poly(ADP-ribosyl)ates Insulin-responsive amino peptidase (IRAP), a resident protein of GLUT4 vesicles, and insulin stimulates the PARP activity of tankyrase1 through its phosphorylation by mitogen-activated protein kinase (MAPK). ADP-ribosylation is a posttranslational modification that usually results in a loss of protein activity presumably by enhancing protein turnover. However, little information is available regarding the physiological function(s) of tankyrase1 other than as a PARP enzyme. In the present study, we found tankyrasel as a specific-binding protein of Mcl-1 Overexpression of tankyrasel led to the inhibition of both the apoptotic activity of Mel-lS and the survival action of Mcl-lL in mammalian cells. Unlike other known tankyrasel-interacting proteins, tankyrasel did not poly(ADP-ribosyl)ate either of the Mcl-1 proteins despite its ability to decrease Mcl-1 proteins expression following coexpression. Therefore, this study provides a novel mechanism to regulate Mcl-1-modulated apoptosis in which tankyrasel downregulates the expression of Mcl-1 proteins without the involvement of its ADP-ribosylation activity.

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Effect of Bisphenol A on Insulin-Mediated Glucose Metabolism In Vivo and In Vitro

  • Ko, Jeong-Hyeon;Kang, Ju-Hee;Park, Chang-Shin;Shin, Dong-Wun;Kim, Ji-Hye;Kim, Hoon;Han, Seung-Baik
    • Molecular & Cellular Toxicology
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    • v.4 no.4
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    • pp.348-354
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    • 2008
  • Bisphenol A (BPA), an environmental endocrine disrupter, enters the human body continuously in food and drink. Young children are likely to be more vulnerable than adults to chemical exposure due to the immaturities of their organ systems, rapid physical development, and higher ventilation, metabolic rates, and activity levels. The direct effect of BPA on peripheral tissue might also be of importance to the development of insulin resistance. However, the influence that BPA has on insulin signaling molecules in skeletal muscle has not been previously investigated. In this study, we examined the effect of BPA on fasting blood glucose (FBG) in post-weaned Wistar rats and on insulin signaling proteins in C2C12 skeletal muscle cells. Subsequently, we investigated the effects of BPA on insulin-mediated Akt phosphorylation in C2C12 myotubes. In rats, BPA treatment (0.1-1,000 ng/mL for 24 hours) resulted in the increase of FBG and plasma insulin levels, and reduced insulin-mediated Akt phosphorylation. Furthermore, the mRNA expression of insulin receptor (IR) was decreased after 24 hours of BPA treatment in C2C12 cells in a dose-dependent manner, whereas the mRNA levels of other insulin signaling proteins, including insulin receptor substrate-1 (IRS-1) and 5'-AMP-dependent protein kinase (AMPK), were unaffected. Treatment with BPA increased GLUT4 expression and protein tyrosine phosphatase 1B (PTP1B) activity in C2C12 myotubes, but not in protein levels. We conclude that exposure to BPA can induce insulin resistance by decreasing IR gene expression, which is followed by a decrease in insulin- mediated Akt activation and increased PTP1B activity.

The Development Properties of Sericin Jam and Composition of Amino Acid in Hemolymph (세리신잠(Nd-s)의 발육특성과 혈액아미노산 조성)

  • Kim, Jong-Hyun;Sohn, Hae-Ryong
    • Current Research on Agriculture and Life Sciences
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    • v.20
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    • pp.55-63
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    • 2002
  • This experiment was to know properties of Sericin Jam that development, growth of silkgland, content of sericin and composition of amino acid in hemolymph. The characters of Sericin Jam can he seen form this experiment. Hatching ratio was 85% in Sericin Jam and 95% in Jam 120. Especially hatching period of Sericin Jam was longer than Jam 120 and also hatching of Sericin Jam was ununiform. The larval duration of Sericin Jam was 20 days and 23 hours, and Jaw 120 was 21 days and 22 hours. In Sericin Jam, middle silkgland contain a great p arts in silkgalod and posterior silkgand is short and no curves. The period of mounting to emergence was 12 days in Sericin Jam. The period of pupa was 7day. It is property of Sericin Jam that the period is short. Cocoon was very thin and light in Sericin Jam. Weight of cocoon shell of Sericin Jam is 2.7cg. The sericin protein quantity was 100% in cocoon shell of Sericin Jam, about 28% in cocoon shell of Jam 120, however the sericin ratio per Sericin Jam cocoon was 34.6% compare to cocoon shell of Jaw 120 in sericin protein quantity. The amino acids in hemolymph of Sericin Jaw was much hidtidine, lysine, glut amic acid. And the amount of almost amino acids were increased depends upon development at t he 5th instar.

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A Research Program for Modeling Strategic Aspects of International Container Port Competition

  • Anderson, Christopher M.;Luo, Meifeng;Chang, Young-Tae;Lee, Tae-Woo;Grigalunas, Thomas A.
    • Proceedings of the Korea Port Economic Association Conference
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    • 2006.08a
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    • pp.1-12
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    • 2006
  • As national economies globalize, demand for intercontinental container shipping services is growing rapidly, providing a potential economic boon for the countries and communities that provide port services. On the promise of profits, many governments are investing heavily in port infrastructure, leading to a possible glut in port capacity, driving down prices for port services and eliminating profits as ports compete for business. Further, existing ports are making strategic investments to protect their market share, increasing the chance new ports will be overcapitalized and unprofitable. Governments and port researchers need a tool for understanding how local competition in their region will affect demand for port services at their location, and thus better assess the profitability of a prospective port. We propose to develop such a tool by extending our existing simulation model of global container traffic to incorporate demand-side shipper preferences and supply-side strategic responses by incumbent ports to changes in the global port network, including building new ports, scaling up existing ports, and unexpected port closures. We will estimate shipper preferences over routes, port attributes and port services based on US and international shipping data, and redesign the simulation model to maximize the shipper's revealed preference functions rather than simply minimize costs. As demand shifts, competing ports will adjust their pricing (short term) and infrastructure (long term) to remain competitive or defend market share, a reaction we will capture with a game theoretic model of local monopoly that will predict changes in port characteristics. The model's hypotheses will be tested in a controlled laboratory experiment tailored to local port competition in Asia, which will also serve to demonstrate the subtle game theoretic concepts of imperfect competition to a policy and industry audience. We will apply the simulation model to analyze changes in global container traffic in three scenarios: addition of a new large port in the US, extended closure of an existing large port in the US, and cooperative and competitive port infrastructure development among Korean partner countries in Asia.

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Dietary zinc supplementation in high-fat diet-induced obese mice: Effects on the skeletal muscle ZIP7 expression and blood glucose regulation (고지방식이 유도 비만 마우스에서 아연 보충이 골격 근육의 아연 수송체 ZIP7 수준과 혈당 조절에 미치는 영향)

  • Zhu, Qianjing;Chung, Jayong
    • Journal of Nutrition and Health
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    • v.54 no.6
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    • pp.594-602
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    • 2021
  • Purpose: The zinc transporter ZIP7 is known to regulate glucose metabolism in skeletal muscles, and skeletal muscles are known to play a critical role in glycemic control. The present study examines the effects of dietary zinc supplementation on the blood glucose concentration and expression of ZIP7 in skeletal muscle obtained from obese mice fed a high-fat diet (HF). Methods: C57BL/6J male mice were divided into three groups and were administered either a HF (60% of total calories from fat), HF supplemented with zinc (HF+Zn, 60% calories from fat + 300 mg zinc/kg diet), or low-fat diet (CON, 10% calories from fat), for 15 weeks. Results: Compared to CON group mice, the final body weights and adipose tissue weights were significantly increased, while the skeletal muscle weights were significantly decreased in mice belonging to the HF and HF+Zn groups. The HF+Zn group had significantly lower levels of fasting blood glucose concentrations than the HF group. Similarly, zinc supplementation significantly decreased the HF-elevated area under the curve values obtained from the oral glucose tolerance test. Skeletal muscle protein levels of ZIP7 in samples obtained from the HF group were significantly decreased as compared to the CON group. Conversely, the skeletal ZIP7 protein levels in the HF+Zn group were significantly increased as compared to the HF group. Moreover, the protein levels of phosphorylated-AKT and glucose transporter 4 in the skeletal muscle were significantly increased subsequent to zinc supplementation. Conclusion: Our data demonstrates that zinc supplementation up-regulates the skeletal muscle ZIP7 expression, which is associated with improved glucose tolerance in the obesity.