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Article: A glimpse of the connection between PPARγ and macrophage.

Yu, Lexiang / Gao, Yuen / Aaron, Nicole / Qiang, Li

2023 Volume 14, Page(s) 1254317

Abstract: Nuclear receptors are ligand-regulated transcription factors that regulate vast cellular activities and serve as an important class of drug targets. Among them, peroxisome proliferator-activated receptors (PPARs) are members of the nuclear receptor ... ...

Abstract	Nuclear receptors are ligand-regulated transcription factors that regulate vast cellular activities and serve as an important class of drug targets. Among them, peroxisome proliferator-activated receptors (PPARs) are members of the nuclear receptor family and have been extensively studied for their roles in metabolism, differentiation, development, and cancer, among others. Recently, there has been considerable interest in understanding and defining the function of PPARs and their agonists in regulating innate and adaptive immune responses and their pharmacological potential in combating chronic inflammatory diseases. In this review, we focus on emerging evidence for the potential role of PPARγ in macrophage biology, which is the prior innate immune executive in metabolic and tissue homeostasis. We also discuss the role of PPARγ as a regulator of macrophage function in inflammatory diseases. Lastly, we discuss the possible application of PPARγ antagonists in metabolic pathologies.
Language	English
Publishing date	2023-08-28
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2587355-6
ISSN	1663-9812
ISSN	1663-9812
DOI	10.3389/fphar.2023.1254317
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Article ; Online: Deciphering the decline of metabolic elasticity in aging and obesity.

Zhou, Qiuzhong / Yu, Lexiang / Cook, Joshua R / Qiang, Li / Sun, Lei

Cell metabolism

2023 Volume 35, Issue 9, Page(s) 1661–1671.e6

Abstract: Organisms must adapt to fluctuating nutrient availability to maintain energy homeostasis. Here, we term the capacity for such adaptation and restoration "metabolic elasticity" and model it through ad libitum-fasting-refeeding cycles. Metabolic elasticity ...

Abstract	Organisms must adapt to fluctuating nutrient availability to maintain energy homeostasis. Here, we term the capacity for such adaptation and restoration "metabolic elasticity" and model it through ad libitum-fasting-refeeding cycles. Metabolic elasticity is achieved by coordinate versatility in gene expression, which we call "gene elasticity." We have developed the gene elasticity score as a systematic method to quantify the elasticity of the transcriptome across metabolically active tissues in mice and non-human primates. Genes involved in lipid and carbohydrate metabolism show high gene elasticity, and their elasticity declines with age, particularly with PPARγ dysregulation in adipose tissue. Synchronizing PPARγ activity with nutrient conditions through feeding-timed agonism optimizes their metabolic benefits and safety. We further broaden the conceptual scope of metabolic and gene elasticity to dietary challenges, revealing declines in diet-induced obesity similar to those in aging. Altogether, our findings provide a dynamic perspective on the dysmetabolic consequences of aging and obesity.
MeSH term(s)	Animals ; Mice ; Obesity/metabolism ; Obesity/pathology ; Gene Expression ; Lipid Metabolism ; Carbohydrate Metabolism ; Macaca fascicularis ; Aging/metabolism ; Aging/pathology ; Fasting ; PPAR gamma/metabolism ; Adipose Tissue/metabolism ; Adaptation, Physiological ; Energy Metabolism ; Male ; Mice, Inbred C57BL
Chemical Substances	PPAR gamma
Language	English
Publishing date	2023-08-24
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	2176834-1
ISSN	1932-7420 ; 1550-4131
ISSN (online)	1932-7420
ISSN	1550-4131
DOI	10.1016/j.cmet.2023.08.001
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Article ; Online: Near-Infrared Responsive Droplet for Digital PCR.

Zhang, Lexiang / Rokshana, Parvin / Yu, Yunru / Zhao, Yuanjin / Ye, Fangfu

Small (Weinheim an der Bergstrasse, Germany)

2022 Volume 18, Issue 16, Page(s) e2107858

Abstract: Digital PCR (dPCR) surpasses the performance of earlier PCR formats because of highly precise, absolute quantification and other unique merits. A simple thermocycling approach and durable microcarrier are of great value for dPCR advancement and ... ...

Abstract	Digital PCR (dPCR) surpasses the performance of earlier PCR formats because of highly precise, absolute quantification and other unique merits. A simple thermocycling approach and durable microcarrier are of great value for dPCR advancement and application. Herein, a near-infrared (NIR) controlled thermocycling approach by embedding magnetic graphene oxide (GO) composite into the agarose microcarriers is developed. The core-shell composite is constructed by sequentially encapsulating GO and silica outside the magnetic nanocores. Benefiting from these additives, the resultant composite agarose gains appealing features as light-driven temperature changing, switchable gel-sol phase transforming, biocompatibility, and magnetic traction. By further emulsifying into droplets via the microfluidics method, the influence of typical parameters including material loading amount, laser intensity, and droplet diameter at various ranges is investigated for assembling microcarriers with different responsiveness. Then a paradigm of the NIR program can be easily tailored for PCR thermocycling. Finally, the feasibility of the approach is verified by detecting statistically diluted Klebsiella pneumoniae DNA samples, from 0.1 to 2 copies per drop. It is anticipated that this method has promising prospects for dPCR-based and other temperature-controlled applications.
MeSH term(s)	DNA ; Microfluidics ; Polymerase Chain Reaction/methods ; Sepharose
Chemical Substances	DNA (9007-49-2) ; Sepharose (9012-36-6)
Language	English
Publishing date	2022-02-25
Publishing country	Germany
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2168935-0
ISSN	1613-6829 ; 1613-6810
ISSN (online)	1613-6829
ISSN	1613-6810
DOI	10.1002/smll.202107858
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Article ; Online: Bicarbonate enhanced heterogeneous activation of peroxymonosulfate by copper ferrite nanoparticles for the efficient degradation of refractory organic contaminants in water.

Cai, Chun / Liu, Yangfan / Xu, Rui / Zhou, Jiaheng / Zhang, Jin / Chen, Yu / Liu, Lingyu / Zhang, Lexiang / Kang, Shuping / Xie, Xianjun

Chemosphere

2022 Volume 312, Issue Pt 1, Page(s) 137285

Abstract: Nowadays, the treatment of residual refractory organic contaminants (ROCs) is a huge challenge for environmental remediation. In this study, a potential process is provided by copper ferrite catalyst ( ... ...

Abstract	Nowadays, the treatment of residual refractory organic contaminants (ROCs) is a huge challenge for environmental remediation. In this study, a potential process is provided by copper ferrite catalyst (CuFe
Language	English
Publishing date	2022-11-17
Publishing country	England
Document type	Journal Article
ZDB-ID	120089-6
ISSN	1879-1298 ; 0045-6535 ; 0366-7111
ISSN (online)	1879-1298
ISSN	0045-6535 ; 0366-7111
DOI	10.1016/j.chemosphere.2022.137285
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Article ; Online: Polycationic PAMAM ameliorates obesity-associated chronic inflammation and focal adiposity

Huang, Baoding / Wan, Qianfen / Li, Tianyu / Yu, Lexiang / Du, Wen / Calhoun, Carmen / Leong, Kam W. / Qiang, Li

Biomaterials. 2023 Feb., v. 293 p.121850-

2023

Abstract: As a surging public health crisis, obesity and overweight predispose individuals to various severe comorbidities contributed by the accompanying chronic inflammation. However, few options exist for tackling chronic inflammation in obesity or inhibiting ... ...

Abstract	As a surging public health crisis, obesity and overweight predispose individuals to various severe comorbidities contributed by the accompanying chronic inflammation. However, few options exist for tackling chronic inflammation in obesity or inhibiting depot-specific adiposity. Here, we report that polycationic polyamidoamine (PAMAM) treatment can improve both aspects of obesity. With the discovery that the plasma cell-free RNA (cfRNA) level is elevated in obese subjects, we applied the cationic PAMAM generation 3 (P-G3) scavenger to treat diet-induced obese (DIO) mice. Intraperitoneal delivery of P-G3 alleviated the chronic inflammation in DIO mice and reduced their body weight, resulting in improved metabolic functions. To further enhance the applicability of P-G3, we complexed P-G3 with human serum albumin (HSA) to attain a sustained release, which showed consistent benefits in treating DIO mice. Local injection of HSA-PG3 into subcutaneous fat completely restricted the distribution of the complex within the targeted depot and reduced focal adiposity. Our study illuminates a promising cationic strategy to ameliorate chronic inflammation in obesity and target local adiposity.
Keywords	RNA ; adiposity ; biocompatible materials ; human serum albumin ; inflammation ; obesity ; public health ; subcutaneous fat ; Polycationic PAMAM ; Chronic inflammation ; Local fat reduction ; Metabolic diseases
Language	English
Dates of publication	2023-02
Publishing place	Elsevier Ltd
Document type	Article ; Online
ZDB-ID	603079-8
ISSN	0142-9612
ISSN	0142-9612
DOI	10.1016/j.biomaterials.2022.121850
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: PPARγ Acetylation in Adipocytes Exacerbates BAT Whitening and Worsens Age-Associated Metabolic Dysfunction.

He, Ying / Zhang, Ruotong / Yu, Lexiang / Zahr, Tarik / Li, Xueming / Kim, Tae-Wan / Qiang, Li

Cells

2023 Volume 12, Issue 10

Abstract: Aging and obesity are the two prominent driving forces of metabolic dysfunction, yet the common underlying mechanisms remain elusive. PPARγ, a central metabolic regulator and primary drug target combatting insulin resistance, is hyperacetylated in both ... ...

Abstract	Aging and obesity are the two prominent driving forces of metabolic dysfunction, yet the common underlying mechanisms remain elusive. PPARγ, a central metabolic regulator and primary drug target combatting insulin resistance, is hyperacetylated in both aging and obesity. By employing a unique adipocyte-specific PPARγ acetylation-mimetic mutant knock-in mouse model, namely aKQ, we demonstrate that these mice develop worsened obesity, insulin resistance, dyslipidemia, and glucose intolerance as they age, and these metabolic deregulations are resistant to intervention by intermittent fasting. Interestingly, aKQ mice show a whitening phenotype of brown adipose tissue (BAT) manifested in lipid filling and suppressed BAT markers. Diet-induced obese aKQ mice retain an expected response to thiazolidinedione (TZD) treatment, while BAT function remains impaired. This BAT whitening phenotype persists even with the activation of SirT1 through resveratrol treatment. Moreover, the adverse effect of TZDs on bone loss is exacerbated in aKQ mice and is potentially mediated by their increased Adipsin levels. Our results collectively suggest pathogenic implications of adipocyte PPARγ acetylation, contributing to metabolic dysfunction in aging and thus posing as a potential therapeutic target.
MeSH term(s)	Animals ; Mice ; Acetylation ; Adipocytes/metabolism ; Adipose Tissue, Brown/metabolism ; Insulin Resistance ; Obesity/metabolism ; PPAR gamma/metabolism
Chemical Substances	PPAR gamma ; Pparg protein, mouse
Language	English
Publishing date	2023-05-18
Publishing country	Switzerland
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2661518-6
ISSN	2073-4409 ; 2073-4409
ISSN (online)	2073-4409
ISSN	2073-4409
DOI	10.3390/cells12101424
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Article: Study of Bond-Slip Behavior and Constitutive Model of a New M-Section Steel-Skeleton Concrete.

Wei, Jun / Yang, Qingshun / Yu, Yang / Wang, Qing / Zhou, Lexiang / Chen, Fei

Materials (Basel, Switzerland)

2022 Volume 15, Issue 19

Abstract: In this study, the bond-slip behavior between a new type of M-section steel skeleton (i.e., M-section steel) applied in assembled shear wall structures and concrete was investigated. First, push-out tests were conducted on 21 M-section steel-concrete ( ... ...

Abstract	In this study, the bond-slip behavior between a new type of M-section steel skeleton (i.e., M-section steel) applied in assembled shear wall structures and concrete was investigated. First, push-out tests were conducted on 21 M-section steel-concrete (MSSC) specimens, wherein the effects of the concrete cover, concrete strength, and anchorage length on the bond strength between the M-section steel and concrete were considered. Further, the crack patterns, strain distribution of M-section steel, and bond-slip curves of the MSSC specimens were investigated using conventional strain measurement and a non-contact optical three-dimensional deformation measurement system, Digital Image Correlation-3D (DIC-3D). The experimental results demonstrated that the bond-slip curves of the MSSC specimens were divided into four stages: the linear ascending, non-linear ascending, non-linear descending, and residual stages. The initial average bond strength τ¯s was mainly affected by the concrete strength and anchorage length, whereas the concrete cover and anchorage length influenced the residual average bond strength τ¯r, and the ultimate average bond strength τ¯u was affected by the concrete strength, concrete cover, and anchorage length. Consequently, a bond-slip constitutive model of M-section steel and concrete was proposed based on the experimental results, and consistency was observed in comparison with the test results, which verified the applicability of the proposed model. Furthermore, to verify the rationality of the bond-slip constitutive model, a numerical simulation was performed, wherein the bond-slip curves, stress clouds, and interfacial bond damage process of the MSSC specimens were investigated. The numerical simulation results indicated that the bond-slip constitutive model could accurately predict the entire failure process of the MSSC specimens.
Language	English
Publishing date	2022-09-29
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2487261-1
ISSN	1996-1944
ISSN	1996-1944
DOI	10.3390/ma15196776
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Article ; Online: Acetylation of PPARγ in macrophages promotes visceral fat degeneration in obesity.

Aaron, Nicole / Zahr, Tarik / He, Ying / Yu, Lexiang / Mayfield, Brent / Pajvani, Utpal B / Qiang, Li

Life metabolism

2022 Volume 1, Issue 3, Page(s) 258–269

Abstract: Obesity is characterized by chronic, low-grade inflammation, which is driven by macrophage infiltration of adipose tissue. PPARγ is well established to have an anti-inflammatory function in macrophages, but the mechanism that regulates its function in ... ...

Abstract	Obesity is characterized by chronic, low-grade inflammation, which is driven by macrophage infiltration of adipose tissue. PPARγ is well established to have an anti-inflammatory function in macrophages, but the mechanism that regulates its function in these cells remains to be fully elucidated. PPARγ undergoes post-translational modifications (PTMs), including acetylation, to mediate ligand responses, including on metabolic functions. Here, we report that PPARγ acetylation in macrophages promotes their infiltration into adipose tissue, exacerbating metabolic dysregulation. We generated a mouse line that expresses a macrophage-specific, constitutive acetylation-mimetic form of PPARγ (
Language	English
Publishing date	2022-11-11
Publishing country	England
Document type	Journal Article
ISSN	2755-0230
ISSN (online)	2755-0230
DOI	10.1093/lifemeta/loac032
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Article ; Online: IgG is an aging factor that drives adipose tissue fibrosis and metabolic decline.

Yu, Lexiang / Wan, Qianfen / Liu, Qiongming / Fan, Yong / Zhou, Qiuzhong / Skowronski, Alicja A / Wang, Summer / Shao, Zhengping / Liao, Chen-Yu / Ding, Lei / Kennedy, Brian K / Zha, Shan / Que, Jianwen / LeDuc, Charles A / Sun, Lei / Wang, Liheng / Qiang, Li

Cell metabolism

2024 Volume 36, Issue 4, Page(s) 793–807.e5

Abstract: Aging is underpinned by pronounced metabolic decline; however, the drivers remain obscure. Here, we report that IgG accumulates during aging, particularly in white adipose tissue (WAT), to impair adipose tissue function and metabolic health. Caloric ... ...

Abstract	Aging is underpinned by pronounced metabolic decline; however, the drivers remain obscure. Here, we report that IgG accumulates during aging, particularly in white adipose tissue (WAT), to impair adipose tissue function and metabolic health. Caloric restriction (CR) decreases IgG accumulation in WAT, whereas replenishing IgG counteracts CR's metabolic benefits. IgG activates macrophages via Ras signaling and consequently induces fibrosis in WAT through the TGF-β/SMAD pathway. Consistently, B cell null mice are protected from aging-associated WAT fibrosis, inflammation, and insulin resistance, unless exposed to IgG. Conditional ablation of the IgG recycling receptor, neonatal Fc receptor (FcRn), in macrophages prevents IgG accumulation in aging, resulting in prolonged healthspan and lifespan. Further, targeting FcRn by antisense oligonucleotide restores WAT integrity and metabolic health in aged mice. These findings pinpoint IgG as a hidden culprit in aging and enlighten a novel strategy to rejuvenate metabolic health.
MeSH term(s)	Mice ; Animals ; Adipose Tissue ; Aging/metabolism ; Adipose Tissue, White/metabolism ; Mice, Knockout ; Fibrosis ; Immunoglobulin G
Chemical Substances	Immunoglobulin G
Language	English
Publishing date	2024-02-19
Publishing country	United States
Document type	Journal Article
ZDB-ID	2176834-1
ISSN	1932-7420 ; 1550-4131
ISSN (online)	1932-7420
ISSN	1550-4131
DOI	10.1016/j.cmet.2024.01.015
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Article ; Online: Adipsin deficiency does not impact atherosclerosis development in

Liu, Longhua / Chan, Michelle / Yu, Lexiang / Wang, Weidong / Qiang, Li

American journal of physiology. Endocrinology and metabolism

2020 Volume 320, Issue 1, Page(s) E87–E92

Abstract: Obesity is a potent risk factor for atherosclerotic morbidity and mortality. Cytokines secreted from adipose tissue, namely, adipokines, have been suggested to be actively involved in atherosclerosis. One of the most abundant adipokines, adipsin, is ... ...

Abstract	Obesity is a potent risk factor for atherosclerotic morbidity and mortality. Cytokines secreted from adipose tissue, namely, adipokines, have been suggested to be actively involved in atherosclerosis. One of the most abundant adipokines, adipsin, is downregulated in obesity. It catalyzes the rate-limiting step of alternative complement activation, which is one of the three complement pathways potentially involved in inflammation in atherosclerosis. Interestingly, adipsin has been identified as a novel biomarker in human coronary artery disease. However, its role in the development of atherosclerosis remains unexplored. We crossed
MeSH term(s)	Adipokines/genetics ; Adipokines/physiology ; Animals ; Aorta/pathology ; Atherosclerosis/genetics ; Atherosclerosis/metabolism ; Body Weight ; Cholesterol, Dietary/pharmacology ; Complement Factor D/deficiency ; Complement Factor D/genetics ; Complement System Proteins/metabolism ; Diet, High-Fat ; Insulin Resistance/genetics ; Lipids/blood ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Plaque, Atherosclerotic/pathology ; Receptors, LDL/deficiency ; Receptors, LDL/genetics
Chemical Substances	Adipokines ; Cholesterol, Dietary ; Lipids ; Receptors, LDL ; Complement System Proteins (9007-36-7) ; Complement Factor D (EC 3.4.21.46) ; complement factor D, mouse (EC 3.4.21.46)
Language	English
Publishing date	2020-11-02
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	603841-4
ISSN	1522-1555 ; 0193-1849
ISSN (online)	1522-1555
ISSN	0193-1849
DOI	10.1152/ajpendo.00440.2020
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