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Induction of thermogenic adipocytes: molecular targets and thermogenic small molecules
송노준,장서혁,Dean Y Li,Claudio J Villanueva,박계원 생화학분자생물학회 2017 Experimental and molecular medicine Vol.49 No.-
Adipose tissue is a central metabolic organ that controls energy homeostasis of the whole body. White adipose tissue (WAT) stores excess energy in the form of triglycerides, whereas brown adipose tissue (BAT) dissipates energy in the form of heat through mitochondrial uncoupling protein 1 (Ucp1). A newly identified adipose tissue called ‘beige fat’ (BAT-like) is produced through a process called WAT browning. This tissue mainly resides in WAT depots and displays intermediate characteristics of both WAT and BAT. Since the recent discovery of BAT in the human body, along with the identification of molecular targets for BAT activation, stimulating energy expenditure has been considered as a great strategy to treat human obesity and metabolic diseases. Here we summarize recent findings regarding molecular targets and thermogenic small molecules that can stimulate BAT and increase energy expenditure, with an emphasis on possible therapeutic applications in humans.
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장재율,장서혁,송다운,송노준,한새로아름,오승준,윤의정,안지인,이석찬,구진모,박계원 한국식품영양과학회 2021 Journal of medicinal food Vol.24 No.12
Butea monosperma (Lam.) Taub. has been applied to treat inflammatory, metabolic, and infectious diseases. However, the antiobesity effects of B. monosperma (Lam.) Taub. flower (BMF) and the underlying mechanisms have not been determined. In this study, we analyzed the various extraction procedures, investigated the antiobesity effects, and identified the main chemical constituents of BMF. The BMF was subjected to acid hydrolysis in 5% H2SO4 in methanol at 50°C for 48 h and partitioned with ethyl acetate. The acid-hydrolyzed BMF ethyl acetate extracts (BMFE) strongly induced the expression of uncoupling protein 1 (Ucp1) and other thermogenic genes in C3H10T1/2 adipocytes. Daily oral administration of 70 mg/kg BMFE (BMFE70) to mice with diet-induced obesity resulted in less body weight gain, increased glucose tolerance, higher rectal temperature, and increased oxygen consumption. Qualitative and quantitative analyses along with treatments in Akt1 knockout mouse embryonic fibroblasts indicate that butein is a major active ingredient of BMFE, which stimulates Ucp1 gene expression. These data show the effects of butein-containing B. monosperma flower extract on thermogenesis and energy expenditure, further suggesting the potential role of BMFE as a functional ingredient in obesity and related metabolic diseases.
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Sulfuretin Prevents Obesity and Metabolic Diseases in Diet Induced Obese Mice
김수지,송노준,장서혁,반가희,최유리,이동권,윤의정,최진희,이전,유재혁,신동한,박기문,강희,이석찬,구진모,조윤신,박계원 한국응용약물학회 2019 Biomolecules & Therapeutics(구 응용약물학회지) Vol.27 No.1
The global obesity epidemic and associated metabolic diseases require alternative biological targets for new therapeutic strategies. In this study, we show that a phytochemical sulfuretin suppressed adipocyte differentiation of preadipocytes and administration of sulfuretin to high fat diet-fed obese mice prevented obesity and increased insulin sensitivity. These effects were associated with a suppressed expression of inflammatory markers, induced expression of adiponectin, and increased levels of phosphorylated ERK and AKT. To elucidate the molecular mechanism of sulfuretin in adipocytes, we performed microarray analysis and identified activating transcription factor 3 (Atf3) as a sulfuretin-responsive gene. Sulfuretin elevated Atf3 mRNA and protein levels in white adipose tissue and adipocytes. Consistently, deficiency of Atf3 promoted lipid accumulation and the expression of adipocyte markers. Sulfuretin’s but not resveratrol’s anti-adipogenic effects were diminished in Atf3 deficient cells, indicating that Atf3 is an essential factor in the effects of sulfuretin. These results highlight the usefulness of sulfuretin as a new anti-obesity intervention for the prevention of obesity and its associated metabolic diseases.
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당귀(Angelica gigas N.)와 토사자(Cuscuta chinensis Lam.)를 포함하는 생약 복합 추출물의 폐경 동물모델에서의 갱년기 증상 완화 효과
김수지(Suji Kim ),장병현(Byung-Hyun Jang),장서혁(Seo-Hyuk Chang),강희(Hee Kang),박기문(Ki-Moon Park),안덕균(Duk Kyun Ahn),김수현(Soohyun Kim),김선미(Sunmi Kim),서대방(Daebang Seo),신송석(Song Seok Shin),박계원(Kye Won Park) 한국식품영양과학회 2016 한국식품영양과학회지 Vol.45 No.8
대부분의 여성은 폐경 이후 신체적 변화를 겪게 된다. 폐경의 증상으로는 홍조, 발한, 몸무게의 증가와 질 건조증 등이 있다. 본 연구에서는 여성의 폐경기 증상 완화에 효능이 있는 열 가지 종류의 생약을 조합하여 만든 혼합 추출물이 동물의 폐경 모델인 난소절제(ovariectomized, OVX) 레트에 어떠한 영향을 미치는지 알아보고자 하였다. 경구투여를 통해 각각 500 mg/kg/d, 1,000 mg/kg/d 농도의 열수 추출물(자음미단)을 8주간 섭취시켰으며, 양성대조군으로 에스트라디올(50 μg/mL)을 사용하였다. 실험을 통해 자음미단이 난소절제 레트에서 몸무게를 유의적으로 감소시켰으며, 간에서의 지방 함량 증가를 억제함을 확인하였다. 자음미단의 섭취는 페경 후 증가하는 혈액의 중성지방과 콜레스테롤 수치도 감소시켰다. 또한, 자음미단은 질의 무게를 증가시켰으며, 특히 질 내벽의 상피세포의 두께에 영향을 주었다. 자음미단의 1,000 mg/kg/d의 농도에서는 에스트로디올과 유사한 정도의 내벽 두께를 관찰할 수 있었다. 따라서 본 실험을 통해 자음미단이 폐경기 여성의 증상인 비만, 대사질환 및 질 건조증의 증상을 완화해줄 수 있으며, 이를 활용한 기능성 식품의 개발이 기대된다. During menopause, elderly woman experience physical and emotional symptoms, including hot flashes, night sweats, weight gain, vaginal dryness, and mood swings. In this study, we investigated the effects of mixed herbal extracts containing Angelica gigas Nakai and Cuscuta chinensis Lam. on menopause symptoms in ovariectomized (OVX) rats. Daily oral treatments of 500 mg/kg and 1,000 mg/kg in OVX rats for 8 weeks significantly reduced weight gain, inhibited hepatic lipid accumulation, and lowered serum lipid levels comparable to the effects induced by estradiol treatments. Mixed herbal extracts (named Jaeummidan) also prevented vaginal dryness as measured by increased vaginal weight. Increased vaginal weight was associated with enlarged epithelium thickness. These data show the preventive actions of Jaeummidan against menopause symptoms and further suggest the possibility of developing functional ingredients in elderly human populations experiencing menopause symptoms.
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