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  • 1
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    A novel AMPK activator, WS070117, improves lipid metabolism discords in hamsters and HepG2 cells
    Springer Science and Business Media LLC ; 2011
    In:  Lipids in Health and Disease Vol. 10, No. 1 ( 2011-12)
    Details
    In: Lipids in Health and Disease, Springer Science and Business Media LLC, Vol. 10, No. 1 ( 2011-12)
    Abstract: WS070117 is a novel small molecule compound that significantly improves lipid metabolism disorders in high-fat-diet (HFD) induced hyperlipidemia in hamsters. Methods and Results We evaluated liver/body weight ratio, liver histology, serum and hepatic lipid content in HFD-fed hamsters treated with WS070117 for 8 weeks. Comparing with HFD fed hamsters, WS070117 (2 mg/kg per day and above) reduced serum triglyceride (TAG), total cholesterol (TC), low density lipoprotein cholesterol (LDL-C) and hepatic cholesterol and triglyceride contents. Oil Red O staining of liver tissue also showed that WS070117 improved lipid accumulation. We then carried out an experiment in the oleic acid (OLA)-induced steatosis model in HepG2 cell to investigate the lipid-lowering effect of WS070117. Oleic acid (0.25 mM) markedly induced lipid accumulation in HepG2 cells, but WS070117 (10 μM) inhibited cellular lipid accumulation. In OLA-treated HepG2 cells, WS070117 (above 1 μM) treatment reduced lipid contents which synthesized from [1- 14 C] labeled acetic acid. Because WS070117 is an analog of adenosine, we evaluated the effect of WS070117 on AMP-activated protein kinase (AMPK) signaling. The results showed that the activation of AMPK in OLA-induced steatosis in HepG2 cells was up-regulated by treatment with 0.1, 1 and 10 μM WS070117. The hepatic cellular AMPK phosphorylation is also up regulated by WS070117 (6 and 18 mg/kg) treatment in HFD fed hamsters. Conclusion These new findings identify WS070117 as a novel molecule that regulates lipid metabolism in the hyperlipidemia hamster model. In vitro and in vivo studies suggested that WS070117 may regulate lipid metabolism through stimulating the activation of AMPK and its downstream pathways.
    Type of Medium: Online Resource
    ISSN: 1476-511X
    URL: Article
    DOI: 10.1186/1476-511X-10-67
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2011
    detail.hit.zdb_id: 2091381-3
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  • 2
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    Abstract 593: High-Monounsaturated Fat Mediterranean-Type Diet Reduces Foamy Monocyte Formation and Atherosclerosis in Ldlr-/- Mice on High-Cholesterol Diet
    Ovid Technologies (Wolters Kluwer Health) ; 2017
    In:  Arteriosclerosis, Thrombosis, and Vascular Biology Vol. 37, No. suppl_1 ( 2017-05)
    Details
    In: Arteriosclerosis, Thrombosis, and Vascular Biology, Ovid Technologies (Wolters Kluwer Health), Vol. 37, No. suppl_1 ( 2017-05)
    Abstract: A large randomized clinical trial (PREDIMED) showed that adding “healthy monounsaturated fat (MUF)” to Mediterranean diet (MedD) by supplementation with extra virgin olive oil or nuts led to a reduction in atherosclerotic cardiovascular events, but the mechanisms remain incompletely understood. Hyperlipidemia, a major risk factor for atherosclerosis, may induce lipid accumulation in circulating monocytes, leading to formation of foamy monocytes (FMs), which contribute to atherosclerosis. We hypothesize that high-MUF MedD reduces FM formation and therefore inhibits atherogenesis associated with hyperlipidemia. To test this, LDLR-/- mice were fed western-type high-saturated fat, high-cholesterol diet (WD) (21% milkfat containing 13.3% saturated fat and 5.9% MUF; 0.2% cholesterol), high-MUF MedD with high cholesterol (HC-MedD, 21% fat [from extra-virgin olive oil, walnuts, almonds, and hazelnuts] containing 2.6% saturated fat and 13.4% MUF; 0.2% cholesterol), or normal diet (ND, control). At 3 months, mice on HC-MedD had similar body weight gain but significantly lower liver/body weight index compared to mice on WD. Plasma triglyceride levels were significantly lower in mice on HC-MedD (318 ± 31 mg/dL, n=13) than on WD (769 ± 60 mg/dL, n=9, P 〈 0.05 vs HC-MedD group). Total cholesterol levels tended to be lower in mice on HC-MedD (2088 ± 180 mg/dL) than on WD (3092 ± 220 mg/dL). Compared to mice on WD, mice on HC-MedD had lower proportions of FMs and lower side scatter values (491 ± 11 vs 555 ± 3 in WD group, n=10/group, P 〈 0.001), indicating less lipid, in FMs. Lipid accumulation in FMs of LDLR-/- on WD accelerated conversion of monocyte subsets from CD11c-CD36+ to CD11c+CD36+, leading to increased ratio of CD11c+CD36+ to CD11c-CD36+ monocytes in mice on WD (2.6 ± 0.3, n=10) vs ND (1.3 ± 0.2, n=9, P 〈 0.01). In contrast, this ratio was not increased in mice on HC-MedD (1.4 ± 0.1, n=10) compared to mice on ND, and was lower than that in mice on WD (P 〈 0.01). Oil red O staining of en face aorta showed 27% decrease in lesion areas in mice on HC-MedD vs on WD (P 〈 0.05). In summary, compared to WD high in saturated fat and cholesterol, high-MUF MedD with high cholesterol lowered triglyceride levels, inhibited FM formation, and reduced atherosclerotic lesion size in LDLR-/- mice.
    Type of Medium: Online Resource
    ISSN: 1079-5642 , 1524-4636
    URL: Article
    DOI: 10.1161/atvb.37.suppl_1.593
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2017
    detail.hit.zdb_id: 1494427-3
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  • 3
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    Abstract 598: Monounsaturated Fat Reduces Foamy Monocyte Formation and Atherosclerosis Development in Ldlr -/- Mice Compared to Western High Saturated Fat Diet
    Ovid Technologies (Wolters Kluwer Health) ; 2018
    In:  Arteriosclerosis, Thrombosis, and Vascular Biology Vol. 38, No. Suppl_1 ( 2018-05)
    Details
    In: Arteriosclerosis, Thrombosis, and Vascular Biology, Ovid Technologies (Wolters Kluwer Health), Vol. 38, No. Suppl_1 ( 2018-05)
    Abstract: Monounsaturated fat (MUF)-rich Mediterranean-type diet (MedD) has been reported to improve atherosclerotic outcome in clinical studies, but the underlying mechanism is ill defined. Circulating foamy monocytes (FMs, monocytes with intracellular lipid droplets), which are CD11c + and highly adherent to inflamed endothelium, contribute to atherosclerosis development. In the present study, we investigated the influence of MedD on FM formation and its contribution to atherosclerosis in mice. LDLR -/- mice were fed MedD with high cholesterol (MedD [w/w, 21% total fat from olive oil and nut] containing 2.6% saturated fat and 13.4% MUF; 0.2% cholesterol) or western diet (WD, 21% milkfat-containing 13.3% saturated fat and 5.9% MUF; 0.2% cholesterol), with normal diet (ND) as control. Lesion area of the whole aorta examined by oil red staining at 3 months was significantly reduced in mice on MedD, compared to WD. Although plasma triglyceride levels were lower in mice on MedD than on WD, the free fatty acid profile indicated that MUFs concentration in plasma significantly increased in mice on MedD. Further, FMs from mice on MedD circulated at lower proportions and exhibited lower side scatter (SSC) than WD, indicating less lipid accumulation. Lipid accumulation in FMs from mice on WD accelerated their conversion from CD11c - /CD36 + to CD11c + /CD36 + compared to mice on ND. In contrast, this accelerated conversion did not occur in mice on MedD. Compared to WD, MedD reduced the number of firmly arrested CD11c + monocytes on vascular cell adhesion molecule-1 and E-selectin coated coverslips detected in an ex-vivo shear flow assay. Similarly, fewer CD11c + macrophages were observed in the lesion of aortic sinus in mice on MedD than on WD. In summary, compared to WD high in saturated fat and cholesterol, MedD high in MUF and cholesterol lowered triglyceride levels, inhibited foamy monocyte formation and adhesion, and reduced atherosclerosis in LDLR -/- mice.
    Type of Medium: Online Resource
    ISSN: 1079-5642 , 1524-4636
    URL: Article
    DOI: 10.1161/atvb.38.suppl_1.598
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2018
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  • 4
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    Abstract 562: Foamy Monocytes in Hypertriglyceridemia
    Ovid Technologies (Wolters Kluwer Health) ; 2018
    In:  Arteriosclerosis, Thrombosis, and Vascular Biology Vol. 38, No. Suppl_1 ( 2018-05)
    Details
    In: Arteriosclerosis, Thrombosis, and Vascular Biology, Ovid Technologies (Wolters Kluwer Health), Vol. 38, No. Suppl_1 ( 2018-05)
    Abstract: Objective: Hypertriglyceridemia (HTG) increases risk for atherosclerotic cardiovascular disease, but the mechanisms remain poorly defined. Foamy monocytes are lipid-loaded monocytes in circulation that contribute to atherosclerosis under hypercholesterolemia. Human study has proved that HTG is associated with formation of foamy monocytes. Our study is to examine formation of foamy monocytes in HTG and their potential contribution to atherosclerosis in mouse models. Approach and results: In vivo mouse models of HTG included wild-type C57BL/6 mice on high fat diet (HFD) injected intraperitoneally with LPL inhibitor, Poloxamer 407 (P407, 0.25mg/g, every two days), as a chemically-induced model and mice with transgenic overexpression of human ApoCIII (ApoCIIItg) as a genetic model. Based on CD11c and CD36, monocytes were identified as CD36 - CD11c - , CD36 + CD11c - and CD36 + CD11c + subsets. In the first model, at 24h of the first injection, triglyceride levels increased to 367 ±84 mg/dL, higher than that of control group with saline injection (60 ±22 mg/dL, n=4, P 〈 0.001). Meanwhile, the side scatter (SSC, representing cell granularity) values and Nile red staining for lipids of CD36 + CD11c + monocytes increased significantly, indicating formation of foamy monocytes, in mice with HTG. Furthermore, CD11c mean fluorescence intensity of CD36 + CD11c + foamy monocytes increased significantly at 2 weeks of P407 injection. In ApoCIIItg mice fed HFD (5 weeks), the percentage and SSC value of CD36 + CD11c + monocytes increased significantly (37%±5%, 247±8), also indicating elevated granularity and lipid accumulation of these monocytes, compared to wild-type mice (26%±3%, p 〈 0.05; 226±8, p 〈 0.05, n=4-6). In vitro treatment with human triglyceride-rich lipoprotein (hTGRL) for 24h increased the granularity and Nile red staining intensity of THP-1 monocytes, indicating foamy monocyte formation. hTGRL treatment also increased THP-1 monocyte expression of CD36, with greater uptake of cholesteryl ester-rich lipoprotein. Conclusion: High triglyceride promotes foamy monocyte formation and induces monocyte phenotypic changes in mice and tissue culture, with increased expression of CD11c and CD36, which may contribute to development of atherosclerosis under HTG.
    Type of Medium: Online Resource
    ISSN: 1079-5642 , 1524-4636
    URL: Article
    DOI: 10.1161/atvb.38.suppl_1.562
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2018
    detail.hit.zdb_id: 1494427-3
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  • 5
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    Poloxamer 407 Induces Hypertriglyceridemia but Decreases Atherosclerosis in Ldlr−/− Mice
    MDPI AG ; 2022
    In:  Cells Vol. 11, No. 11 ( 2022-05-30), p. 1795-
    Details
    In: Cells, MDPI AG, Vol. 11, No. 11 ( 2022-05-30), p. 1795-
    Abstract: Background: Hypertriglyceridemia (HTG) increases the risk for atherosclerotic cardiovascular disease, but underlying mechanisms are incompletely understood. Circulating monocytes play an important role in atherogenesis by infiltrating arterial walls, where they differentiate into macrophages. We tested the hypothesis that HTG is mechanistically linked to atherogenesis by altering the monocyte phenotype and infiltration into atherosclerotic lesions in a model of diet-induced atherogenesis in Ldlr−/− mice. Methods: HTG was induced in male Ldlr−/− mice, fed a Western, high-fat high-cholesterol diet, by daily injection of poloxamer 407 (P407), a lipoprotein lipase inhibitor, for seven weeks. Atherosclerosis, monocyte phenotypes, and monocyte migration into atherosclerotic lesions were determined by well-validated methods. Results: Compared with the saline control, P407 injection in Ldlr−/− mice rapidly induced profound and persistent HTG, modestly elevated plasma cholesterol levels, and increased levels of triglyceride and cholesterol carried in very-low-density lipoprotein and low-density lipoprotein. Unexpectedly, mice receiving P407 versus saline control showed less atherosclerosis. Following induction of HTG by P407, CD36+ (also CD11c+), but not CD36− (CD11c−), monocytes showed early increases in lipid accumulation, but the number of CD36+ (not CD36−) monocytes was dramatically decreased afterwards in the circulation until the end of the test. Concurrently, CD36+ (CD11c+) monocyte migration into atherosclerotic lesions was also reduced in mice receiving P407 versus controls. Conclusions: P407 induced severe HTG, but reduced atherosclerosis, in Ldlr−/− mice, possibly because of profound reductions of circulating CD36+ (CD11c+) monocytes, leading to decreased monocyte migration into atherosclerotic lesions.
    Type of Medium: Online Resource
    ISSN: 2073-4409
    URL: Article
    DOI: 10.3390/cells11111795
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2661518-6
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  • 6
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    1990-P: STAT1 Knockdown in CD11c+ Cells Prevents Adipose Tissue Inflammation and Metabolic Dysfunction in Mice on High-Fat Diet
    American Diabetes Association ; 2019
    In:  Diabetes Vol. 68, No. Supplement_1 ( 2019-06-01)
    Details
    In: Diabetes, American Diabetes Association, Vol. 68, No. Supplement_1 ( 2019-06-01)
    Abstract: Background: Classically activated M1-like CD11c+ macrophages/dendritic cells (MDCs) are increased in obese adipose tissue (AT) and may contribute to AT inflammation and the development of insulin resistance in obesity. STAT1 is a key transcription factor for MDC polarization into M1-like phenotypes. Here, we examined the role of STAT1 in obesity-induced AT MDC polarization and inflammation and insulin resistance in mice. Methods: Mice with specific knockout (KO) of STAT1 in CD11c+ MDCs were generated by crossbreeding STAT1fl/fl and CD11c-Cre mice. CD11c/STAT1 KO and littermate controls were fed high-fat diet (HFD, 16 weeks) to induce obesity and evaluated for immune cells and browning/beige adipogenesis in perigonadal (pAT) and inguinal (iAT) AT and metabolic functions. Results: Compared to control mice, KO mice on HFD had similar body weight. Analyses of AT immune cells revealed that compared to controls, KO mice had a decrease in M1-like proinflammatory polarization but an increase in M2-like polarization of macrophages and reduced CD8+ T cell number in pAT, and significant increases in the proportion of IL-5+ Th2 cells and eosinophils (CD170+) in pAT and iAT (p & lt;0.05). Furthermore, compared to control mice, KO mice showed significantly increased iAT expression of browning markers (Ucp-1, Cidea, and prdm16) and had increased oxygen consumption rate but lower respiratory exchange ratio, indicating higher energy expenditure and increased fat utilization as energy source. Moreover, KO mice, as compared to controls, had significant reductions in triglyceride content in the liver and skeletal muscle and exhibited improved insulin sensitivity and glucose tolerance examined by insulin and glucose tolerance test (p & lt;0.05). Conclusion: STAT1 plays an important role in obesity-induced MDC M1-like polarization and AT inflammation and contributes to insulin resistance and metabolic dysfunctions in obese mice. Disclosure A. Kalathookunnel Antony: None. X. Perrard: None. Z. Lian: None. J. Perrard: None. C.M. Ballantyne: Consultant; Self; Abbott, Akcea Therapeutics, Amarin Corporation, Amgen Inc., AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Esperion, Gilead Sciences, Inc., Matinas BioPharma, Merck & Co., Inc., Novartis Pharmaceuticals Corporation, Novo Nordisk Inc., Regeneron Pharmaceuticals, Roche Diagnostic USA, Sanofi. Research Support; Self; Abbott, Akcea Therapeutics, Amarin Corporation, Amgen Inc., Esperion, Novartis Pharmaceuticals Corporation, Regeneron Pharmaceuticals, Roche Diagnostic USA, Sanofi. Other Relationship; Self; Roche Diagnostic USA. H. Wu: None. Funding American Diabetes Association (1-17-IBS-082 to H.W.)
    Type of Medium: Online Resource
    ISSN: 0012-1797 , 1939-327X
    URL: Article
    DOI: 10.2337/db19-1990-P
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 2019
    detail.hit.zdb_id: 1501252-9
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  • 7
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    Applications of Higenamine in pharmacology and medicine
    Elsevier BV ; 2017
    In:  Journal of Ethnopharmacology Vol. 196 ( 2017-01), p. 242-252
    Details
    In: Journal of Ethnopharmacology, Elsevier BV, Vol. 196 ( 2017-01), p. 242-252
    Type of Medium: Online Resource
    ISSN: 0378-8741
    URL: Article
    DOI: 10.1016/j.jep.2016.12.033
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2017
    detail.hit.zdb_id: 1491279-X
    SSG: 15,3
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  • 8
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    A Systematic, Integrated Study on the Neuroprotective Effects of Hydroxysafflor Yellow A Revealed by H 1 NMR-Based Metabonomics and the NF- κ B Pathway
    Hindawi Limited ; 2013
    In:  Evidence-Based Complementary and Alternative Medicine Vol. 2013 ( 2013), p. 1-14
    Details
    In: Evidence-Based Complementary and Alternative Medicine, Hindawi Limited, Vol. 2013 ( 2013), p. 1-14
    Abstract: Hydroxysafflor yellow A (HSYA) is the main active component of the Chinese herb Carthamus tinctorius L.. Purified HSYA is used as a neuroprotective agent to prevent cerebral ischemia. Injectable safflor yellow (50 mg, containing 35 mg HSYA) is widely used to treat patients with ischemic cardiocerebrovascular disease. However, it is unknown how HSYA exerts a protective effect on cerebral ischemia at the molecular level. A systematical integrated study, including histopathological examination, neurological evaluation, blood-brain barrier (BBB), metabonomics, and the nuclear factor- κ B (NF- κ B) pathway, was applied to elucidate the pathophysiological mechanisms of HSYA neuroprotection at the molecular level. HSYA could travel across the BBB, significantly reducing the infarct volume and improving the neurological functions of rats with ischemia. Treatment with HSYA could lead to relative corrections of the impaired metabolic pathways through energy metabolism disruption, excitatory amino acid toxicity, oxidative stress, and membrane disruption revealed by 1 H NMR-based metabonomics. Meanwhile, HSYA treatment inhibits the NF- κ B pathway via suppressing proinflammatory cytokine expression and p65 translocation and binding activity while upregulating an anti-inflammatory cytokine.
    Type of Medium: Online Resource
    ISSN: 1741-427X , 1741-4288
    URL: Article
    DOI: 10.1155/2013/147362
    Language: English
    Publisher: Hindawi Limited
    Publication Date: 2013
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  • 9
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    144-OR: The Antirheumatic Drug Auranofin Improves the Metabolic Phenotype of Obesity
    American Diabetes Association ; 2020
    In:  Diabetes Vol. 69, No. Supplement_1 ( 2020-06-01)
    Details
    In: Diabetes, American Diabetes Association, Vol. 69, No. Supplement_1 ( 2020-06-01)
    Abstract: Obesity is associated with chronic low-grade inflammation, reflecting significant alterations in the composition of immune cell populations that reside in white adipose tissue (WAT). The ensuing pro-inflammatory environment likely impinges on the metabolic functions of adipocytes and may partially explain the insulin resistance that characterizes type 2 diabetes mellitus (T2DM). We recently demonstrated ectopic expression of the microRNA miR-30a in the subcutaneous fat pad of diabetic mice coupled improved insulin sensitivity and increased energy expenditure with decreased ectopic fat deposition in the liver and reduced WAT inflammation. We subsequently pursued the notion that pharmacological inhibitors of inflammation that exhibit a gene expression profile similar to ectopic miR-30a expression in WAT should represent new drugs for insulin resistance and T2DM. To this end, we used the Broad Connectivity Map to analyze a library of small molecules that induce mRNA profiles similar to that of exogenous miR-30a expression in WAT. Through this process, we nominated the rheumatoid arthritis compound auranofin. Treatment of obese mice with auranofin improved insulin sensitivity and glucose tolerance. Auranofin treatment also normalized other obesity-associated abnormalities, including hepatic steatosis, serum insulin and leptin. Mechanistically, a combination of proteomics and immunophenotyping established auranofin likely exerts antidiabetic activities by opposing low-grade inflammation in WAT and ectopic liver fat accumulation. These studies reveal important metabolic properties of anti-inflammatory treatments that may be re-purposed as therapies for insulin resistance and T2DM. Disclosure A. Cox: None. P.M. Masschelin: None. N. Chernis: None. P. Saha: None. Z. Lian: None. J.B. Felix: None. K. Kim: None. H. Wu: None. S.M. Hartig: None. Funding American Diabetes Association (1-18-IBS-105 to S.M.H.); National Institutes of Health (R01DK114356)
    Type of Medium: Online Resource
    ISSN: 0012-1797 , 1939-327X
    URL: Article
    DOI: 10.2337/db20-144-OR
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 2020
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  • 10
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    1205-P: Baricitinib Inhibition of Jak/STAT Pathway Changed Immune Composition in Adipose Tissue and Improved Metabolism in Diet-Induced Obese Mice
    American Diabetes Association ; 2021
    In:  Diabetes Vol. 70, No. Supplement_1 ( 2021-06-01)
    Details
    In: Diabetes, American Diabetes Association, Vol. 70, No. Supplement_1 ( 2021-06-01)
    Abstract: Jak/STAT pathway plays key roles in inflammation and is highly activated in adipose tissue (AT) in obesity. Recently, inhibition of the Jak/STAT pathway with baricitinib, a Jak1/Jak2 inhibitor, has been demonstrated to accelerate clinical improvements in a trial of hospitalized patients with COVID-19, who had a mean BMI of 32. Currently, we aimed to examine effects of long-term treatment with baricitinib on AT inflammation and metabolism in diet-induced obese mice. Starting from 3 months old, male C57BL/6J mice were fed high fat diet (HFD) and concurrently received daily oral gavage of baricitinib (10mg/kg) or vehicle for 12 weeks. Compared to vehicle control, baricitinib treatment significantly improved insulin resistance examined by insulin tolerance test and increased UCP1 (a key browning marker) expression in perigonadal (pAT) and inguinal AT (iAT), but did not affect weight gain and AT mass. Strikingly, total T cells were reduced by ~50% in iAT and pAT in baricitinib group vs. control group. CD4+ IFNγ-expressing Th1 cells, IL5-expressing Th2 cells, and TNFα-expressing T cells were decreased in pAT, but not in iAT, of mice from baricitinib group vs. control group. Unexpectedly, percentage of TNFα-expressing cells in CD8+ T cells were higher in iAT of baricitinib-treated mice than controls. Finally, baricitinib compared to control reduced M1/M2 ratio in pAT, but not iAT, and reduced eosinophils in iAT and pAT. Baricitinib inhibition of Jak/STAT pathway in diet-induced obese mice improved insulin sensitivity and changed immune cells in AT, with dramatic reductions of T cells in particular, indicating an important role of Jak/STAT-mediated inflammation in metabolism in obesity. Given the fact that obesity and insulin resistance are associated with increased severity of COVID-19, our data also point to the need for further studies on AT immune cells, COVID-19, and baricitinib. Disclosure Z. Lian: None. X. Perrard: None. C. M. Ballantyne: Advisory Panel; Self; Amarin Corporation plc, Arrowhead Pharmaceuticals, Inc., Pfizer Inc., Consultant; Self; Amgen Inc., CSL Behring, Intercept Pharmaceuticals, Inc., Novartis Pharmaceuticals Corporation, Novo Nordisk, Regeneron Pharmaceuticals Inc., Research Support; Self; Abbott, Amgen Inc., Ionis Pharmaceuticals, Novartis Pharmaceuticals Corporation, Regeneron Pharmaceuticals Inc., Roche Diagnostic USA. H. Wu: None.
    Type of Medium: Online Resource
    ISSN: 0012-1797 , 1939-327X
    URL: Article
    DOI: 10.2337/db21-1205-P
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 2021
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