• 제목/요약/키워드: Obesity-related genes

검색결과 136건 처리시간 0.028초

Protein Tyrosine Phosphatase, Receptor Type B (PTPRB) Inhibits Brown Adipocyte Differentiation through Regulation of VEGFR2 Phosphorylation

  • Kim, Ji Soo;Kim, Won Kon;Oh, Kyoung-Jin;Lee, Eun-Woo;Han, Baek Soo;Lee, Sang Chul;Bae, Kwang-Hee
    • Journal of Microbiology and Biotechnology
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    • 제29권4호
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    • pp.645-650
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    • 2019
  • Brown adipocytes have an important role in the regulation of energy balance through uncoupling protein-1 (UCP-1)-mediated nonshivering thermogenesis. Although brown adipocytes have been highlighted as a new therapeutic target for the treatment of metabolic diseases, such as obesity and type II diabetes in adult humans, the molecular mechanism underlying brown adipogenesis is not fully understood. We recently found that protein tyrosine phosphatase receptor type B (PTPRB) expression dramatically decreased during brown adipogenic differentiation. In this study, we investigated the functional roles of PTPRB and its regulatory mechanism during brown adipocyte differentiation. Ectopic expression of PTPRB led to a reduced brown adipocyte differentiation by suppressing the tyrosine phosphorylation of VEGFR2, whereas a catalytic inactive PTPRB mutant showed no effects on differentiation and phosphorylation. Consistently, the expression of brown adipocyte-related genes, such as UCP-1, $PGC-1{\alpha}$, PRDM16, $PPAR-{\gamma}$, and CIDEA, were significantly inhibited by PTPRB overexpression. Overall, these results suggest that PTPRB functions as a negative regulator of brown adipocyte differentiation through its phosphatase activity-dependent mechanism and may be used as a target protein for the regulation of obesity and type II diabetes.

Effect of cinacalcet-mediated parathyroid hormone reduction on vitamin D metabolism in high-fat diet-induced obese mice

  • Tae Yeon Kim;Chan Yoon Park;Sung Nim Han
    • Journal of Nutrition and Health
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    • 제56권1호
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    • pp.1-11
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    • 2023
  • Purpose: Obesity is associated with alterations in vitamin D metabolism and elevation of parathyroid hormone (PTH). Increased PTH level in obesity is likely one of the factors contributing to the dysregulation of vitamin D metabolism. We investigated the effects of lowering the PTH level in high-fat diet-induced obese mice on vitamin D metabolism. Methods: Five-week-old male C57BL/6N mice were fed either with control (10% energy as fat) or high-fat (60% energy as fat) diets ad libitum for 12 weeks, and vehicle or cinacalcet HCl (30 ㎍/g body weight) was gavaged daily during the final week of the experiment. The following groups were studied: CON (control diet + vehicle), HFD (high-fat diet + vehicle), and HFD-CIN (high-fat diet + cinacalcet HCl). PTH, 1,25-dihydroxyvitamin D (1,25[OH]2D), 25-hydroxyvitamin D (25[OH]D), calcium, and phosphate levels in circulation, and the expression of genes related to vitamin D metabolism in the liver and kidneys were determined. Results: Renal 1α-hydroxylase expression in the HFD group was higher than that in the CON group despite the lack of a difference in the PTH levels between the 2 groups. The plasma PTH level in the HFD-CIN group was 60% lower than that in the HFD group (p < 0.05). In parallel, the HFD-CIN group had lower adipose tissue amount (9% lower), renal 1α-hydroxylase expression (48% lower), and plasma 1,25(OH)2D concentration (38% lower) than the HFD group. Conclusion: Lowering the PTH levels in high-fat diet-induced obese mice recovered the expression of renal 1α-hydroxylase and might be associated with lower amounts of white adipose tissue.

Issues in Adults Prader-Willi Syndrome

  • Park, Sung Won
    • Journal of mucopolysaccharidosis and rare diseases
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    • 제1권2호
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    • pp.40-43
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    • 2015
  • Prader-Willi syndrome (PWS), a complex genetic disorder, arises from suppressed expression of paternally inherited imprinted genes on chromosome 15q11-q13. Characteristics include short stature, intellectual disability, behavioral problems, hypogonadism, obesity, and reduced bone and muscle. The life expectancy of persons with PWS has increased in recent years. Cardiovascular diseases, diabetes, dermatological, and orthopedic problems are common physical complaints in older people with PWS. Behavioral problems are major concerns in adults with PWS into old age. And aging is also associated with significant social and economic changes. Age-related physical morbidity, physical appearance, behavioral and psychiatric problems, functional decline and economic problems can be combined in older PWS. The care for older people with PWS requires a life span approach that recognizes the presence, progression, and consequences of specific morbidity.

A Brief Review of Preclinical Researches and Clinical Trials of Oxytocin on Behavior-Related Phenotypes in Prader-Willi Syndrome

  • Kim, Jiyeon
    • Journal of mucopolysaccharidosis and rare diseases
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    • 제5권1호
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    • pp.39-41
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    • 2021
  • Prader-Willi syndrome (PWS) is a rare genetic neurodevelopmental disorder of hyperphagia leading to severe obesity, intellectual deficits, compulsivity, and other behavioral problems. PWS is caused by the inactivation of contiguous genes on chromosome 15q11-q13, which complicates the development of targeted, effective therapeutics. Various preclinical studies have been conducted by developing mouse models that exhibit phenotypes similar to PWS. Oxytocin deficiency in PWS is associated with hyperphagia with impaired satiety and, food-seeking and behavior disorders. Here, we summarize the oxytocin study of ingestion behavior tested in the PWS mouse model and published data from clinical trials that have evaluated treatment effectiveness on ingestion behavior and social dysfunction in patients with PWS.

댕댕이나무 열매 추출물이 지방전구세포와 마우스 지방유래줄기세포의 분화 및 지방 생성 억제에 미치는 영향 (Effects of Lonicera caerulea extract on adipocyte differentiation and adipogenesis in 3T3-L1 cells and mouse adipose-derived stem cells (MADSCs))

  • 박미의;이창호;이해정
    • Journal of Nutrition and Health
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    • 제52권1호
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    • pp.17-25
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    • 2019
  • 본 연구에서는 댕댕이나무 열매 추출물이 3T3-L1과 마우스 지방유래줄기세포의 지방 분화유도 및 지방생성에 미치는 영향을 살펴보았다. 3T3-L1에 댕댕이나무 열매 추출물을 처리하였을 때, 농도의존적으로 지방구의 생성을 줄였고 지방세포 분화에 있어서 중요한 전사인자인 $PPAR{\gamma}$, $C/EBP{\alpha}$, SREBP1의 발현을 억제시켜 지방 합성이 감소됨을 확인하였다. 또한, 마우스 지방에서 분리한 줄기세포의 지방 분화과정에서도 댕댕이나무 열매 추출물이 $PPAR{\gamma}$, $C/EBP{\alpha}$, SREBP1의 단백질 발현을 감소시켜 지방 축적을 농도 의존적으로 억제하였다. 이상의 결과로 댕댕이나무 열매 추출물은 세포독성이 없는 농도에서 지방 세포의 분화를 억제 하는 것으로 확인되어 항비만 기능성 소재로서의 활용 가능성이 있을 것으로 사료된다.

고지방 식이 유도 비만 마우스 모델에서 황정 추출물의 지방질 및 에너지 대사 관련 유전자에 대한 효능 연구 (Effects of Polygonatum sibiricum rhizome extract on lipid and energy metabolism in high-fat diet-induced obese mice)

  • 전우진;김지영;오익훈;이도섭;손서연;서윤지;연승우;강재훈
    • 한국식품과학회지
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    • 제49권2호
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    • pp.192-202
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    • 2017
  • 황정 주정 추출물 ID1216의 고지방 식이 유도 비만 마우스에서의 체중 증가 억제 효과에 대한 분자생물학적 기전을 확인하고자 단백질과 mRNA 수준에서 지질 및 에너지 대사 관련 유전자들의 발현 변화를 관찰하였다. 본 연구에서 확인된 지표들 간의 상호 작용 및 ID1216의 조절 여부에 관해 Fig. 10에 나타내었다. 실험 결과 ID1216은 고지방 식이 유도 비만 마우스에서 체중 증가 억제를 나타내었으며, 비만 대사 관련 pathway의 상위 유전자로 사료되는 SIRT1과 AMPK의 발현을 조절하는 것으로 나타났다. 활성화된 SIRT1과 AMPK는 $PGC1{\alpha}$의 활성화에 관여하고, 이를 통해 열 발산 대사와 관련된 UCP 단백질과 핵 수용체 단백질인 $PPAR{\alpha}$의 발현이 백색지방, 갈색지방, 간 및 근육에서 증가되는 것이 확인되었다. 각 조직 별로 RT-PCR을 진행한 결과에서는 $PPAR{\alpha}$의 하위 유전자인 aP2, ACO, Acadl, Acadm, CPT1a, CPT1b의 mRNA 발현 수준을 향상시켜 주어 ID1216이 지방산 산화 대사인 ${\beta}$-oxidation의 활성화에 기여할 가능성을 보여주었다. 이와는 별개로 ID1216은 중성지질을 분해하는 것으로 알려진 ATGL의 mRNA 발현 또한 증가시키는 것으로 확인되었다. 본 연구를 통해 ID1216이 조직에 따라 지질 및 에너지 대사와 관련된 인자의 발현에 영향을 주는 체중 조절에 효과적인 소재임을 알 수 있었다. 또한 비만 치료제와의 기전적 차별성과 생약 특유의 섭취 안전성을 특징으로 하는 체중 또는 체지방 조절 기능성 소재로의 활용 가능성도 충분히 가지고 있음을 확인할 수 있었다.

대두 이소플라본과 수영운동이 난소절제 쥐의 간 기능 개선에 미치는 시너지 효과 (Synergistic effect of soy isoflavone and swimming exercise on improvement of liver function in ovariectomized mice)

  • 정선효
    • 한국응용과학기술학회지
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    • 제40권4호
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    • pp.589-605
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    • 2023
  • 대두 이소플라본은 갱년기 증상에 대한 유익한 효과 때문에 폐경여성들의 관심을 끌고 있다. 본 연구는 난소절제 쥐에서 대두 이소플라본인 제니스테인과 수영운동의 동시처리(Gen+SE)가 제니스테인 단독처리(Gen)와 수영운동 단독처리(SE)에 비해 비만과 간 기능 개선에 유익한 시너지 효과를 나타낼 것인지를 조사하였다. 난소절제 쥐는 무작위로 대조군(Con), Gen, SE 및 Gen+SE으로 나누어 8주 동안 고지방식이를 섭취하였다. 몸무게, 백색지방조직의 무게, 간 조직의 지질추적 및 혈청 속 ALT와 AST 수치를 조사한 결과, Con에 비해 Gen과 SE는 감소하였고 Gen+SE는 Gen과 SE에 비해 더 효과적으로 감소하였다. 간 조직에서 염증성 사이토카인인 IL-6와 TNF-𝛼 유전자의 발현은 Con에 비해 Gen과 SE 모두에서 감소하였고, Gen+SE는 Gen과 SE에 비해 더욱 감소하였다. 그러나 adiponectin 유전자의 발현은 반대의 결과가 나타났다. 간 조직에서 지방산 산화와 관련된 유전자의 발현은 Con에 비해 Gen과 SE에서 증가하였고 Gen+SE는 Gen과 SE에 비해 더 증가하였다. 따라서 본 연구는 대두 이소플라본과 수영운동의 상호작용은 난소절제 비만 쥐에서 비만 조절과 저하된 간 기능 개선에 매우 효과적이며, 이것은 난소절제 쥐에서 간의 지방산 산화를 촉진함으로써 발생한 것이라는 것을 제안한다.

Potential involvement of Drosophila flightless-1 in carbohydrate metabolism

  • Park, Jung-Eun;Jang, Jinho;Lee, Eun Ji;Kim, Su Jung;Yoo, Hyun Ju;Lee, Semin;Kang, Min-Ji
    • BMB Reports
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    • 제51권9호
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    • pp.462-467
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    • 2018
  • A previous study of ours indicated that Drosophila flightless-1 controls lipid metabolism, and that there is an accumulation of triglycerides in flightless-1 (fliI)-mutant flies, where this mutation triggers metabolic stress and an obesity phenotype. Here, with the aim of characterizing the function of FliI in metabolism, we analyzed the levels of gene expression and metabolites in fliI-mutant flies. The levels of enzymes related to glycolysis, lipogenesis, and the pentose phosphate pathway increased in fliI mutants; this result is consistent with the levels of metabolites corresponding to a metabolic pathway. Moreover, high-throughput RNA sequencing revealed that Drosophila FliI regulates the expression of genes related to biological processes such as chromosome organization, carbohydrate metabolism, and immune reactions. These results showed that Drosophila FliI regulates the expression of metabolic genes, and that dysregulation of the transcription controlled by FliI gives rise to metabolic stress and problems in the development and physiology of Drosophila.

New Evidences of Effect of Melanocortin-4 Receptor and Insulin-like Growth Factor 2 Genes on Fat Deposition and Carcass Traits in Different Pig Populations

  • Chen, J.F.;Xiong, Y.Z.;Zuo, B.;Zheng, R.;Li, F.E.;Lei, M.G.;Li, J.L.;Deng, C.Y.;Jiang, S.W.
    • Asian-Australasian Journal of Animal Sciences
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    • 제18권11호
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    • pp.1542-1547
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    • 2005
  • The Melanocortin-4 Receptor (MC4R) and Insulin-like Growth Factor 2 (IGF2) are two important candidate genes related to fat deposition and carcass traits. MC4R was found on study on human obesity and then was studied as candidate gene affecting food intake and fat deposition traits in mice and pigs. Insulin-like Growth Factor 2 (IGF2) gene plays an important role on tumor cell proliferation and muscle growth. It also affects fat traits and live weight in pigs. In this paper, MC4R and IGF2 were studied as two candidate genes associated with important economic traits such as fat deposition and carcass traits in five different pig populations. Taq I-PCR-RFLP and Bcn I-PCR-RFLP were respectively used to detect the polymorphism of genotypes of MC4R and IGF2 genes. Different MC4R genotype frequencies were observed in four populations. IGF2 genotype frequencies were also different in two populations. The results of association analysis show both MC4R and IGF2 genes were significantly associated with fat deposition and carcass traits in about 300 pigs. This work will add new evidence of MC4R and IGF2 affecting fat deposition and carcass traits in pigs and show that two genes can be used as important candidate genes for marker assistant selection (MAS) of growth and lean meat percentage in pigs.

Biological Effects of Allium monanthum Extracts on Lipid Metabolism, Anti-oxidation and the Production of Pro-inflammatory Cytokines in Rats Fed a High-Fat Diet

  • Yoon, Kwang Ro;Ryu, Jae Kuk;Lee, Eun
    • 한국자원식물학회지
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    • 제26권3호
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    • pp.337-346
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    • 2013
  • This study is a basic study on the development of functional substances involved in obesity prevention, lipid metabolism, and immune regulation. Male Sprague-Dawley rats were fed a high-fat diet for 10 weeks. Allium monanthum extracts (AME) were administered orally to obesity-induced rats, and their lipid-lowering, antioxidative and various types of biological effects related to the immune system were examined. Blood free fatty acid and triglyceride concentrations decreased as the dose of AME increased. Total cholesterol and LDL cholesterol concentrations in the blood decreased as the dose of AME increased. The total cholesterol concentrations in the liver of the AME-treated groups were lower than the control group. The thiobarbituric acid reactive concentrations were lower in the plasma and liver of all AME-treated groups than the control group. Plasma AST and ALT activities did not show any significant differences among the treatment groups. IL-$1{\beta}$ and IL-6 concentrations in the liver tended to decrease as the dose of AME increased. TNF-${\alpha}$ and IL-10 concentrations did now show any significant differences compared to the control group. Lower expression levels of TNF-${\alpha}$, Apo-B and Apo-E genes were found in the AME-treated groups. Taken together, these results indicate that AME may show positive effects in lipid lowering, antioxidation and anti-inflammation.