Liensinine Inhibits Beige Adipocytes Recovering to white Adipocytes through Blocking Mitophagy Flux In Vitro and In Vivo
Identifieur interne : 000690 ( Main/Exploration ); précédent : 000689; suivant : 000691Liensinine Inhibits Beige Adipocytes Recovering to white Adipocytes through Blocking Mitophagy Flux In Vitro and In Vivo
Auteurs : Siyu Xie [République populaire de Chine] ; Yuan Li [République populaire de Chine] ; Wendi Teng [République populaire de Chine] ; Min Du [États-Unis] ; Yixuan Li [République populaire de Chine] ; Baoguo Sun [République populaire de Chine]Source :
- Nutrients [ 2072-6643 ] ; 2019.
Abstract
Promoting white-to-beige adipocyte transition is a promising approach for obesity treatment. Although Liensinine (Lie), a kind of isoquinoline alkaloid, has been reported to affect white-to-beige adipocyte transition, its effects on inhibiting beige adipocytes recovering to white adipocytes and maintaining the characteristics of beige adipocyte remain unclear. Therefore, we explored the effects and underlying mechanism of Lie on beige adipocyte maintenance in vitro and in vivo. Here, we first demonstrated that after white adipocytes turned to beige adipocytes by rosiglitazone (Rosi) stimuli, beige adipocytes gradually lost their characteristics and returned to white adipocytes again once Rosi was withdrawn. We found that Lie retained high levels of uncoupling protein 1 (UCP1) and mitochondrial oxidative phosphorylation complex I, II, III, IV and V (COX I–V), oxygen consumption rate (OCR) after Rosi withdrawal. In addition, after Rosi withdrawal, the beige-to-white adipocyte transition was coupled to mitophagy, while Lie inhibited mitophagy flux by promoting the accumulation of pro-cathepsin B (pro-CTSB), pro-cathepsin D (pro-CTSD) and pro-cathepsin L (pro-CTSL), ultimately maintaining the beige adipocytes characteristics in vitro. Moreover, through blocking mitophagy flux, Lie significantly retained the molecular characteristics of beige adipocyte, reduced body weight gain rate and enhanced energy expenditure after stimuli withdrawal in vivo. Together, our data showed that Lie inhibited lysosomal cathepsin activity by promoting the accumulation of pro-CTSB, pro-CTSD and pro-CTSL, which subsequently inhibited mitophagy flux, and ultimately inhibited the beige adipocytes recovering to white adipocytes and maintained the characteristics of beige adipocyte after stimuli withdrawal. In conclusion, by blocking lysosome-mediated mitophagy, Lie inhibits beige adipocytes recovering to white adipocytes and may be a potential candidate for preventing high fat diet induced obesity.
Url:
DOI: 10.3390/nu11071640
PubMed: 31323747
PubMed Central: 6682930
Affiliations:
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wicri:level="1"><nlm:aff id="af1-nutrients-11-01640">Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Food Science & Nutritional Engineering, China Agricultural University, Beijing100083, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Food Science & Nutritional Engineering, China Agricultural University, Beijing100083</wicri:regionArea><wicri:noRegion>Beijing100083</wicri:noRegion></affiliation></author><author><name sortKey="Li, Yuan" sort="Li, Yuan" uniqKey="Li Y" first="Yuan" last="Li">Yuan Li</name><affiliation wicri:level="1"><nlm:aff id="af1-nutrients-11-01640">Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Food Science & Nutritional Engineering, China Agricultural University, Beijing100083, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Food Science & Nutritional Engineering, China Agricultural University, Beijing100083</wicri:regionArea><wicri:noRegion>Beijing100083</wicri:noRegion></affiliation></author><author><name sortKey="Teng, Wendi" sort="Teng, Wendi" uniqKey="Teng W" first="Wendi" last="Teng">Wendi Teng</name><affiliation wicri:level="1"><nlm:aff id="af1-nutrients-11-01640">Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Food Science & Nutritional Engineering, China Agricultural University, Beijing100083, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Food Science & Nutritional Engineering, China Agricultural University, Beijing100083</wicri:regionArea><wicri:noRegion>Beijing100083</wicri:noRegion></affiliation></author><author><name sortKey="Du, Min" sort="Du, Min" uniqKey="Du M" first="Min" last="Du">Min Du</name><affiliation wicri:level="1"><nlm:aff id="af2-nutrients-11-01640">Department of Animal Sciences, Washington State University, Pullman, Washington, WA 99164, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Animal Sciences, Washington State University, Pullman, Washington, WA 99164</wicri:regionArea><wicri:noRegion>WA 99164</wicri:noRegion></affiliation></author><author><name sortKey="Li, Yixuan" sort="Li, Yixuan" uniqKey="Li Y" first="Yixuan" last="Li">Yixuan Li</name><affiliation wicri:level="1"><nlm:aff id="af1-nutrients-11-01640">Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Food Science & Nutritional Engineering, China Agricultural University, Beijing100083, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Food Science & Nutritional Engineering, China Agricultural University, Beijing100083</wicri:regionArea><wicri:noRegion>Beijing100083</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="af3-nutrients-11-01640">Key Laboratory of Functional Dairy, Co-constructed by ministry of Education and Beijing Municipality, College of Food Science & Nutritional Engineering, China Agricultural University, Beijing100083, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Key Laboratory of Functional Dairy, Co-constructed by ministry of Education and Beijing Municipality, College of Food Science & Nutritional Engineering, China Agricultural University, Beijing100083</wicri:regionArea><wicri:noRegion>Beijing100083</wicri:noRegion></affiliation></author><author><name sortKey="Sun, Baoguo" sort="Sun, Baoguo" uniqKey="Sun B" first="Baoguo" last="Sun">Baoguo Sun</name><affiliation wicri:level="1"><nlm:aff id="af4-nutrients-11-01640">Beijing Technology and Business University, Beijing100083, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Beijing Technology and Business University, Beijing100083</wicri:regionArea><wicri:noRegion>Beijing100083</wicri:noRegion></affiliation></author></analytic><series><title level="j">Nutrients</title><idno type="eISSN">2072-6643</idno><imprint><date when="2019">2019</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Promoting white-to-beige adipocyte transition is a promising approach for obesity treatment. Although Liensinine (Lie), a kind of isoquinoline alkaloid, has been reported to affect white-to-beige adipocyte transition, its effects on inhibiting beige adipocytes recovering to white adipocytes and maintaining the characteristics of beige adipocyte remain unclear. Therefore, we explored the effects and underlying mechanism of Lie on beige adipocyte maintenance in vitro and in vivo. Here, we first demonstrated that after white adipocytes turned to beige adipocytes by rosiglitazone (Rosi) stimuli, beige adipocytes gradually lost their characteristics and returned to white adipocytes again once Rosi was withdrawn. We found that Lie retained high levels of uncoupling protein 1 (UCP1) and mitochondrial oxidative phosphorylation complex I, II, III, IV and V (COX I–V), oxygen consumption rate (OCR) after Rosi withdrawal. In addition, after Rosi withdrawal, the beige-to-white adipocyte transition was coupled to mitophagy, while Lie inhibited mitophagy flux by promoting the accumulation of pro-cathepsin B (pro-CTSB), pro-cathepsin D (pro-CTSD) and pro-cathepsin L (pro-CTSL), ultimately maintaining the beige adipocytes characteristics in vitro. Moreover, through blocking mitophagy flux, Lie significantly retained the molecular characteristics of beige adipocyte, reduced body weight gain rate and enhanced energy expenditure after stimuli withdrawal in vivo. Together, our data showed that Lie inhibited lysosomal cathepsin activity by promoting the accumulation of pro-CTSB, pro-CTSD and pro-CTSL, which subsequently inhibited mitophagy flux, and ultimately inhibited the beige adipocytes recovering to white adipocytes and maintained the characteristics of beige adipocyte after stimuli withdrawal. In conclusion, by blocking lysosome-mediated mitophagy, Lie inhibits beige adipocytes recovering to white adipocytes and may be a potential candidate for preventing high fat diet induced obesity.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Brestoff, J R" uniqKey="Brestoff J">J.R. Brestoff</name></author><author><name sortKey="Artis, D" uniqKey="Artis D">D. Artis</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Khandekar, M J" uniqKey="Khandekar M">M.J. Khandekar</name></author><author><name sortKey="Cohen, P" uniqKey="Cohen P">P. Cohen</name></author><author><name sortKey="Spiegelman, B M" uniqKey="Spiegelman B">B.M. Spiegelman</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zhang, Y" uniqKey="Zhang Y">Y. Zhang</name></author><author><name sortKey="Sowers, J R" uniqKey="Sowers J">J.R. Sowers</name></author><author><name sortKey="Ren, J" uniqKey="Ren J">J. 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Zhao</name></author></analytic></biblStruct></listBibl></div1></back></TEI><affiliations><list><country><li>République populaire de Chine</li><li>États-Unis</li></country></list><tree><country name="République populaire de Chine"><noRegion><name sortKey="Xie, Siyu" sort="Xie, Siyu" uniqKey="Xie S" first="Siyu" last="Xie">Siyu Xie</name></noRegion><name sortKey="Li, Yixuan" sort="Li, Yixuan" uniqKey="Li Y" first="Yixuan" last="Li">Yixuan Li</name><name sortKey="Li, Yixuan" sort="Li, Yixuan" uniqKey="Li Y" first="Yixuan" last="Li">Yixuan Li</name><name sortKey="Li, Yuan" sort="Li, Yuan" uniqKey="Li Y" first="Yuan" last="Li">Yuan Li</name><name sortKey="Sun, Baoguo" sort="Sun, Baoguo" uniqKey="Sun B" first="Baoguo" last="Sun">Baoguo Sun</name><name sortKey="Teng, Wendi" sort="Teng, Wendi" uniqKey="Teng W" first="Wendi" last="Teng">Wendi Teng</name></country><country name="États-Unis"><noRegion><name sortKey="Du, Min" sort="Du, Min" uniqKey="Du M" first="Min" last="Du">Min Du</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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