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학술연구/단체지원/교육 등 연구자 활동을 지속하도록 DBpia가 지원하고 있어요.
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논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 발행연도
- 2018.3
- 수록면
- 244 - 255 (12page)
- DOI
- 10.14348/molcells.2018.2156
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초록· 키워드
오류제보하기
Low-grade pro-inflammatory state and leptin resistance are important underlying mechanisms that contribute to obesityassociated hypertension. We tested the hypothesis that Astragaloside IV (As IV), known to counteract obesity and hypertension, could prevent obesity-associated hypertension by inhibiting pro-inflammatory reaction and leptin resistance. High-fat diet (HFD) induced obese rats were randomly assigned to three groups: the HFD control group (HF con group), As IV group, and the As IV + α-bungaratoxin (α-BGT) group (As IV+α-BGT group). As IV (20 mg·Kg-1·d-1) was administrated to rats for 6 weeks via daily oral gavage. Body weight and blood pressure were continuously measured, and NE levels in the plasma and renal cortex was evaluated to reflect the sympathetic activity. The expressions of leptin receptor (LepRb) mRNA, phosphorylated signal transducer and activator of transcription-3 (p-STAT3), phosphorylated phosphatidylinositol 3-kinase (p-PI3K), suppressor of cytokine signaling 3 (SOCS3) mRNA, and protein-tyrosine phosphatase 1B (PTP1B) mRNA, pro-opiomelanocortin (POMC) mRNA and neuropeptide Y (NPY) mRNA were measured by Western blot or qRT-PCR to evaluate the hypothalamic leptin sensitivity. Additionally, we measured the protein or mRNA levels of α7nAChR, inhibitor of nuclear factor κB kinase subunit β/nuclear factor κB (IKKβ/NF-KB) and pro-inflammatory cytokines (IL-1β and TNF-α) in hypothalamus and adipose tissue to reflect the anti-inflammatory effects of As IV through upregulating expression of α7nAChR. We found that As IV prevented body weight gain and adipose accumulation, and also improved metabolic disorders in HFD rats. Furthermore, As IV decreased BP and HR, as well as NE levels in blood and renal tissue. In the hypothalamus, As IV alleviated leptin resistance as evidenced by the increased p-STAT3, LepRb mRNA and POMC mRNA, and decreased p-PI3K, SOCS3 mRNA, and PTP1B mRNA. The effects of As IV on leptin sensitivity were related in part to the up-regulated α7nAchR and suppressed IKKβ/NF-KB signaling and pro-inflammatory cytokines in the hypothalamus and adipose tissue, since co-administration of α7nAChR selective antagonist α-BGT could weaken the improved effect of As IV on central leptin resistance. Our study suggested that As IV could efficiently prevent obesityassociated hypertension through inhibiting inflammatory reaction and improving leptin resistance; furthermore, these effects of As IV was partly related to the increased α7nAchR expression.
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참고문헌 (52)
참고문헌 신청
Cai, D. / 2009 / NFkappaB-mediated metabolic inflammation in peripheral tissues versus central nervous system / Cell Cycle 8:2542~2548
Cai, D. / 2013 / Neuroinflammation in overnutrition-induced diseases / Vitam. Horm. 91:195~218
Cai, D. / 2011 / Hypothalamic inflammation: a doubleedged sword to nutritional diseases / Ann. N Y Acad. Sci. 1243:E1~E39
Castellano, J.M. / 2014 / An alternative transcription start site yields estrogen-unresponsive Kiss1 mRNA transcripts in the hypothalamus of prepubertal female rats / Neuroendocrinology 99:94~107
Chen, N.Z.Q. / 2006 / Pharmacokinetics and tissue distribution of astragaloside IV in rats / Chin. J. Bioproc. E. 4:67~72
Cai, D. / 2013 / Neuroinflammation in overnutrition-induced diseases / Vitam. Horm. 91:195~218
Cai, D. / 2011 / Hypothalamic inflammation: a doubleedged sword to nutritional diseases / Ann. N Y Acad. Sci. 1243:E1~E39
Castellano, J.M. / 2014 / An alternative transcription start site yields estrogen-unresponsive Kiss1 mRNA transcripts in the hypothalamus of prepubertal female rats / Neuroendocrinology 99:94~107
Chen, N.Z.Q. / 2006 / Pharmacokinetics and tissue distribution of astragaloside IV in rats / Chin. J. Bioproc. E. 4:67~72
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