Liensinine Inhibits Beige Adipocytes Recovering to white Adipocytes through Blocking Mitophagy Flux In Vitro and In Vivo
Identifieur interne : 000819 ( Ncbi/Merge ); précédent : 000818; suivant : 000820Liensinine 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stimuli, beige adipocytes gradually lost their characteristics and returned to white adipocytes again once Rosi was withdrawn.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
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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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<front><journal-meta><journal-id journal-id-type="nlm-ta">Nutrients</journal-id><journal-id journal-id-type="iso-abbrev">Nutrients</journal-id><journal-id journal-id-type="publisher-id">nutrients</journal-id><journal-title-group><journal-title>Nutrients</journal-title></journal-title-group><issn pub-type="epub">2072-6643</issn><publisher><publisher-name>MDPI</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">31323747</article-id><article-id pub-id-type="pmc">6682930</article-id><article-id pub-id-type="doi">10.3390/nu11071640</article-id><article-id pub-id-type="publisher-id">nutrients-11-01640</article-id><article-categories><subj-group subj-group-type="heading"><subject>Article</subject></subj-group></article-categories><title-group><article-title>Liensinine Inhibits Beige Adipocytes Recovering to white Adipocytes through Blocking Mitophagy Flux In Vitro and In Vivo</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Xie</surname><given-names>Siyu</given-names></name><xref ref-type="aff" rid="af1-nutrients-11-01640">1</xref></contrib><contrib contrib-type="author"><name><surname>Li</surname><given-names>Yuan</given-names></name><xref ref-type="aff" rid="af1-nutrients-11-01640">1</xref></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid" authenticated="true">https://orcid.org/0000-0002-4135-8901</contrib-id><name><surname>Teng</surname><given-names>Wendi</given-names></name><xref ref-type="aff" rid="af1-nutrients-11-01640">1</xref></contrib><contrib contrib-type="author"><name><surname>Du</surname><given-names>Min</given-names></name><xref ref-type="aff" rid="af2-nutrients-11-01640">2</xref></contrib><contrib contrib-type="author"><name><surname>Li</surname><given-names>Yixuan</given-names></name><xref ref-type="aff" rid="af1-nutrients-11-01640">1</xref><xref ref-type="aff" rid="af3-nutrients-11-01640">3</xref></contrib><contrib contrib-type="author"><name><surname>Sun</surname><given-names>Baoguo</given-names></name><xref ref-type="aff" rid="af4-nutrients-11-01640">4</xref><xref rid="c1-nutrients-11-01640" ref-type="corresp">*</xref></contrib></contrib-group><aff id="af1-nutrients-11-01640"><label>1</label>Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Food Science & Nutritional Engineering, China Agricultural University, Beijing100083, China</aff><aff id="af2-nutrients-11-01640"><label>2</label>Department of Animal Sciences, Washington State University, Pullman, Washington, WA 99164, USA</aff><aff id="af3-nutrients-11-01640"><label>3</label>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</aff><aff id="af4-nutrients-11-01640"><label>4</label>Beijing Technology and Business University, Beijing100083, China</aff><author-notes><corresp id="c1-nutrients-11-01640"><label>*</label>Correspondence: <email>sunbg@btbu.edu.cn</email>; Tel.: +86-10-68984890</corresp></author-notes><pub-date pub-type="epub"><day>18</day><month>7</month><year>2019</year></pub-date><pub-date pub-type="collection"><month>7</month><year>2019</year></pub-date><volume>11</volume><issue>7</issue><elocation-id>1640</elocation-id><history><date date-type="received"><day>24</day><month>6</month><year>2019</year></date><date date-type="accepted"><day>16</day><month>7</month><year>2019</year></date></history><permissions><copyright-statement>© 2019 by the authors.</copyright-statement><copyright-year>2019</copyright-year><license license-type="open-access"><license-p>Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (<ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by/4.0/">http://creativecommons.org/licenses/by/4.0/</ext-link>).</license-p></license></permissions><abstract><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></abstract><kwd-group><kwd>liensinine</kwd><kwd>beige adipocyte</kwd><kwd>obesity</kwd><kwd>mitophagy</kwd><kwd>cathepsin protein</kwd></kwd-group></article-meta></front><floats-group><fig id="nutrients-11-01640-f001" orientation="portrait" position="float"><label>Figure 1</label><caption><p>Liensinine (Lie) inhibited the beige adipocytes recovering to white adipocytes and retained their characteristics after rosiglitazone (Rosi) withdrawal in vitro. (<bold>A</bold>) Schematic illustration about in vitro experiments. Preadipocytes were differentiated into white adipocytes. Beige adipocytes were induced by treating white adipocytes with 10 μM Rosi for 2 days. After 10μM of Rosi withdrawal, beige adipocytes were exposed to various concentrations (0, 10, 20 and 40 μM) of Lie for 5 days, respectively. (<bold>B</bold>) Immunoblotting for uncoupling protein 1 (UCP1) and mitochondrial oxidative phosphorylation complex I, II, III, IV and V (COX I–V) in the control (0 μM Rosi) and beige adipocytes. (<bold>C</bold>) After Ros withdrawal, immunoblotting for UCP1 and COX I-V at indicated time points (day 0–5)<bold>.</bold> (<bold>D</bold>) Oxygen consumption rate (OCR) in the control, beige adipocytes and beige adipocytes at day 5 following Rosi withdrawal. The mitochondrial complex inhibitors were injected sequentially in the following order: oligomycin (1 μM), carbonyl cyanide 4 (trifluoromethoxy) phenylhydrazone (FCCP) (0.75 μM), antimycin/rotenone (1 μM each). (<bold>E</bold>) Effects of Lie on the viability of beige adipocytes. Beige adipocytes were exposed to various concentrations (0, 10, 20, 40 and 60μM) of Lie for 5 days, respectively. (<bold>F</bold>) Immunoblotting for UCP1 and COX I–V in beige adipocytes exposed to various concentrations (0, 10, 20 and 40 μM) of Lie for 5 days after Rosi withdrawal, respectively. (<bold>G</bold>) OCR in beige adipocytes exposed to various concentrations (0, 10 and 40 μM) of Lie for 5 days after Rosi withdrawal, respectively. Values shown are means ± standard deviation (SD), # <italic>p</italic> < 0.05 vs. 0 μM Rosi group; * <italic>p</italic> < 0.05 vs. 0 μM Lie group.</p></caption><graphic xlink:href="nutrients-11-01640-g001"></graphic></fig><fig id="nutrients-11-01640-f002" orientation="portrait" position="float"><label>Figure 2</label><caption><p>Lie blocked mitophagy after Rosi withdrawal in vitro. After Rosi withdrawal, immunoblotting for microtubule-associated protein 1 light chain 3 (LC3) at indicated time points (day 0–5) (<bold>A</bold>) A densitometric assay of each band. Fold change in optical density relative to day zero in the below of panel of A. After Rosi withdrawal, immunoblotting for selective autophagy adaptor protein (p62) at indicated time points (day 0–5) (<bold>B</bold>) And densitometric assay of each band. Fold change in optical density relative to day zero in the below of panel of <bold>B</bold>. After Rosi withdrawal, beige adipocytes stained with p62 antibodies at indicated time points (<bold>C</bold>) Scale bars, 20 mm. After Rosi withdrawal, beige adipocytes stained with LC3 and Parkin antibodies at indicated time points (<bold>D</bold>) Scale bars, 20 mm. After Rosi withdrawal, beige adipocytes were treated Lie (0, 10, 20 and 40 μM) or chloroquine (CQ, 10μM) for 5 days. Western blot analysis showing the levels of LC3 (<bold>E</bold>) A densitometric assay of each band. Fold change in optical density relative to control (0 μM Lie) in the below of panel of <bold>E</bold>. Western blot analysis showing the levels of p62 (<bold>F</bold>) A densitometric assay of each band. Fold change in optical density relative to control in the below of panel of <bold>F</bold>. Immunoblotting showing the of the levels of p62 (<bold>G</bold>) Scale bars, 20 mm. Values shown are means ± standard deviation (SD), # <italic>p</italic> < 0.05 vs. 0 day after Rosi withdrawal; * <italic>p</italic> < 0.05 vs. 0 μM Lie group.</p></caption><graphic xlink:href="nutrients-11-01640-g002"></graphic></fig><fig id="nutrients-11-01640-f003" orientation="portrait" position="float"><label>Figure 3</label><caption><p>Lie blocked mitophagy flux by impairing the function of lysosomal proteases after Rosi withdrawal in vitro. After Rosi withdrawal, beige adipocytes were subjected to Lie for 5 days. (<bold>A</bold>) Fusion between autophagosomes (anti-LC3) and lysosomes (anti- lysosome-associated membrane protein 2) (anti-LAMP2) was evident in Lie (0 and 40 µM)-treated beige adipocytes (yellow in merged images). Scale bars, 20 mm. Western blot analysis showing the levels of pro-cathepsin B (pro-CTSB), mature-cathepsin B (mat-CTSB), pro-cathepsin D (pro-CTSD), mature-cathepsin D (mat-CTSD), pro-cathepsin L (pro-CTSL) and mature-cathepsin L (mat-CTSL) (<bold>B</bold>) A densitometric assay of each band. Fold change in optical density relative to control group (0 μM Lie) in the right of panel of B. (<bold>C</bold> and <bold>D</bold>) After Rosi withdrawal, beige adipocytes were treated with Lie (0 and 40 µM) for 5 days, which was prepared and subjected to immunostaining with anti-CTSB/anti-CTSD and anti-COX IV. Scale bars, 20 mm. Values shown are means ± standard deviation (SD), * <italic>p</italic> < 0.05 vs. 0 μM group.</p></caption><graphic xlink:href="nutrients-11-01640-g003"></graphic></fig><fig id="nutrients-11-01640-f004" orientation="portrait" position="float"><label>Figure 4</label><caption><p>Lie retained the molecular characteristics of beige adipocytes after β3-AR agonist withdrawal in vivo. (<bold>A</bold>) Schematic illustration about in vivo experiments. Mice were treated with the HFD+β3-AR agonist or high fat diet (HFD+) saline for 7 days consecutively and after β3-AR agonist withdrawal, the mice were treated with HFD + 60 mg·kg<sup>−1</sup> CQ, HFD + 60 mg·kg<sup>−1</sup> Lie or HFD + saline (control), respectively. (<bold>B</bold>) Immunoblotting for uncoupling protein 1 (UCP1) and mitochondrial oxidative phosphorylation complex I–V (COX I–V) in the inguinal white adipocyte tissue (WAT) depots of mice treated with the HFD+β3-AR agonist or HFD + saline for 7 days consecutively. (<bold>C</bold>) Immunoblotting for UCP1 and COX I–V in the inguinal WAT depots of mice at indicated time points after β3-AR agonist withdrawal. (<bold>D</bold>) Mice were treated with the HFD+β3-AR agonist for 7 days consecutively and after β3-AR agonist withdrawal, the mice were treated with HFD + 60 mg·kg<sup>−1</sup> CQ, HFD + 60 mg·kg<sup>−1</sup> Lie or HFD + saline (control), respectively. Inguinal WAT depots were harvested for immunoblotting analyses and immunohistochemical analysis. (<bold>D</bold>) Immunoblotting analyses showing that the levels of UCP1 and COX I–V. (<bold>E</bold>) Immunohistochemical analysis for UCP1, p62, LC3 and mat-CTSB.</p></caption><graphic xlink:href="nutrients-11-01640-g004"></graphic></fig><fig id="nutrients-11-01640-f005" orientation="portrait" position="float"><label>Figure 5</label><caption><p>Lie retained the functional characteristics of beige adipocytes and ameliorated HFD-induced obesity in vivo. Mice were treated with the HFD + β3-AR agonist for 7 days consecutively and after β3-AR agonist withdrawal, the mice were treated with HFD + 60 mg·kg<sup>−1</sup> CQ, HFD + 60 mg·kg<sup>−1</sup> Lie or HFD + saline (control), respectively. Magnetic resonance imaging (MRI) images showing fat distribution in mice (<bold>A</bold>) Fat mass content (<italic>n</italic> = 3/group) (<bold>B</bold>) Inguinal WAT depots were harvested for H&E images (<bold>C</bold>) Quantification of whole-body O<sub>2</sub> consumption, CO<sub>2</sub> production and energy expenditure of mice treated with HFD + 60 mg·kg<sup>−1</sup> CQ, HFD + 60 mg·kg<sup>−1</sup> Lie or HFD + saline for 15 days after β3-AR agonist withdrawal. O<sub>2</sub> consumption, CO<sub>2</sub> production and energy expenditure were measured during a 12 h light-dark cycle (<bold>D</bold>) <italic>n</italic> = 3/group. Values shown are means ± standard deviation (SD), * <italic>p</italic> < 0.05 vs. saline group.</p></caption><graphic xlink:href="nutrients-11-01640-g005"></graphic></fig><table-wrap id="nutrients-11-01640-t001" orientation="portrait" position="float"><object-id pub-id-type="pii">nutrients-11-01640-t001_Table 1</object-id><label>Table 1</label><caption><p>Metabolic characteristics of study mice treated with HFD + 60 mg kg<sup>−1</sup> CQ, HFD + 60 mg kg<sup>−1</sup> Lie or HFD + saline for 15 days after β3-AR agonist withdrawal.</p></caption><table frame="hsides" rules="groups"><thead><tr><th align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Group</th><th align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Saline</th><th align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">60 mg·kg<sup>−1</sup><break></break>CQ</th><th align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">60 mg·kg<sup>−1</sup><break></break>Lie</th></tr></thead><tbody><tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Weight gain rate (%)<break></break>Lean content (%)<break></break>Water content (%)<break></break>TC (mg·dL<sup>−1</sup>)<break></break>TG (mg·dL<sup>−1</sup>)<break></break>LDL-C (mg·dL<sup>−1</sup>)<break></break>HDL-C (mg·dL<sup>−1</sup>)</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">10.70% ± 2.29%<break></break>45.64% ± 0.79%<break></break>5.16% ± 1.73%<break></break>4.82 ± 0.50<break></break>0.92 ± 0.24<break></break>0.36 ± 0.07<break></break>3.83 ± 0.17</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">−4.12% ± 0.92% *<break></break>45.56% ± 2.03%<break></break>4.27% ± 4.27%<break></break>4.38 ± 0.13<break></break>1.01 ± 0.06<break></break>0.38 ± 0.07<break></break>3.20 ± 0.07 *</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">2.71% ± 0.89% *<break></break>46.68% ± 2.80%<break></break>4.67% ± 0.52%<break></break>4.4 ± 0.65<break></break>0.88 ± 0.06 <break></break>0.45 ± 0.32<break></break>3.19 ± 0.13 *</td></tr></tbody></table><table-wrap-foot><fn><p>TC, Serum total cholesterol; TG, Serum triglycerides; LDL-C, Serum low-density-lipoprotein cholesterol; HDL-C, Serum high-density-lipoprotein cholesterol. * indicates a significant difference from the saline group. * <italic>p</italic> < 0.05 vs. saline group.</p></fn></table-wrap-foot></table-wrap></floats-group></pmc><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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