Fibroblast growth factor 1 ameliorates adipose tissue inflammation and systemic insulin resistance via enhancing adipocyte mTORC2/Rictor signal

Zhao, Lingyue; Fan, Miaojuan; Zhao, Lijun; Yun, Hongyan; Yang, Yan; Wang, Chen; Di, Qianqian

doi:10.1111/jcmm.15872

Cited by 12 publications

(6 citation statements)

References 43 publications

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“…This can be counteracted by treatment with recombinant FGF1, which leads to insulin sensitization by increasing insulin-dependent glucose uptake in skeletal muscle and suppressing the hepatic production of glucose (Suh et al, 2014). Mechanistically, this is achieved by inhibition of macrophage recruitment and inflammatory responses in adipose tissue by activation of adipocyte mTORC2/ Rictor signaling and inhibition of C-C chemokine ligand 2 (CCL2) production (L. Zhao, Fan, et al, 2020).…”

Section: Fgf Signaling In Diet-induced Obesitymentioning

confidence: 99%

New developments in the biology of fibroblast growth factors

Ornitz

Itoh

2022

WIREs Mechanisms of Disease

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The fibroblast growth factor (FGF) family is composed of 18 secreted signaling proteins consisting of canonical FGFs and endocrine FGFs that activate four receptor tyrosine kinases (FGFRs 1-4) and four intracellular proteins (intracellular FGFs or iFGFs) that primarily function to regulate the activity of voltagegated sodium channels and other molecules. The canonical FGFs, endocrine FGFs, and iFGFs have been reviewed extensively by us and others. In this review, we briefly summarize past reviews and then focus on new developments in the FGF field since our last review in 2015. Some of the highlights in the past 6 years include the use of optogenetic tools, viral vectors, and inducible transgenes to experimentally modulate FGF signaling, the clinical use of small molecule FGFR inhibitors, an expanded understanding of endocrine FGF signaling, functions for FGF signaling in stem cell pluripotency and differentiation, roles for FGF signaling in tissue homeostasis and regeneration, a continuing elaboration of mechanisms of FGF signaling in development, and an expanding appreciation of roles for FGF signaling in neuropsychiatric diseases.

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Section: Fgf Signaling In Diet-induced Obesitymentioning

confidence: 99%

New developments in the biology of fibroblast growth factors

Ornitz

Itoh

2022

WIREs Mechanisms of Disease

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“…FGF21 is an hepatokine known to improve systemic insulin sensitivity and to promote a favorable metabolic profile in diet-induced obese mice (75). Likewise, FGF1 has been shown to dampen hepatic glucose output by suppressing adipose lipolysis (76), improve systemic insulin sensitivity by reducing adipose inflammation (77), and alleviate hepatic steatosis, inflammation, and insulin resistance (78). Thus, upregulated expression of Fgf21 and Fgf1 in Ctrp10 KO female mice could contribute to the MHO phenotype.…”

Section: Transcriptomic and Pathway Changes Associated With The Metab...mentioning

confidence: 99%

Loss of CTRP10 results in female obesity with preserved metabolic health

Chen,

Sarver,

Saqib

et al. 2023

Preprint

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Obesity is a major risk factor for type 2 diabetes, dyslipidemia, cardiovascular disease, and hypertension. Intriguingly, there is a subset of metabolically healthy obese (MHO) individuals who are seemingly able to maintain a healthy metabolic profile free of metabolic syndrome. The molecular underpinnings of MHO, however, are not well understood. Here, we report that CTRP10/C1QL2-deficient mice represent a unique female model of MHO. CTRP10 modulates weight gain in a striking and sexually dimorphic manner. Female, but not male, mice lacking CTRP10 develop obesity with age on a low-fat diet while maintaining an otherwise healthy metabolic profile. When fed an obesogenic diet, femaleCtrp10knockout (KO) mice show rapid weight gain. Despite pronounced obesity,Ctrp10KO female mice do not develop steatosis, dyslipidemia, glucose intolerance, insulin resistance, oxidative stress, or low-grade inflammation. Obesity is largely uncoupled from metabolic dysregulation in female KO mice. Multi-tissue transcriptomic analyses highlighted gene expression changes and pathways associated with insulin-sensitive obesity. Transcriptional correlation of the differentially expressed gene (DEG) orthologous in humans also show sex differences in gene connectivity within and across metabolic tissues, underscoring the conserved sex-dependent function of CTRP10. Collectively, our findings suggest that CTRP10 negatively regulates body weight in females, and that loss of CTRP10 results in benign obesity with largely preserved insulin sensitivity and metabolic health. This female MHO mouse model is valuable for understanding sex-biased mechanisms that uncouple obesity from metabolic dysfunction.

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“…In humans, body mass index correlates well with adipose tissue CCL2 expression [116,117]. CCL2 has been suggested to influence the function of adipocytes and to be the link between adipose tissue inflammation, insulin resistance, and liver impairment [99,118,119]. The inflammatory reaction induced by CCL2 could contribute to deterioration of cell homeostasis and energy requirements in metabolic organs [53,118].…”

Section: Obesity and The Associated Liver Diseasementioning

confidence: 99%

On the Role of Paraoxonase-1 and Chemokine Ligand 2 (C-C motif) in Metabolic Alterations Linked to Inflammation and Disease. A 2021 Update

et al. 2021

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Infectious and many non-infectious diseases share common molecular mechanisms. Among them, oxidative stress and the subsequent inflammatory reaction are of particular note. Metabolic disorders induced by external agents, be they bacterial or viral pathogens, excessive calorie intake, poor-quality nutrients, or environmental factors produce an imbalance between the production of free radicals and endogenous antioxidant systems; the consequence being the oxidation of lipids, proteins, and nucleic acids. Oxidation and inflammation are closely related, and whether oxidative stress and inflammation represent the causes or consequences of cellular pathology, both produce metabolic alterations that influence the pathogenesis of the disease. In this review, we highlight two key molecules in the regulation of these processes: Paraoxonase-1 (PON1) and chemokine (C-C motif) ligand 2 (CCL2). PON1 is an enzyme bound to high-density lipoproteins. It breaks down lipid peroxides in lipoproteins and cells, participates in the protection conferred by HDL against different infectious agents, and is considered part of the innate immune system. With PON1 deficiency, CCL2 production increases, inducing migration and infiltration of immune cells in target tissues and disturbing normal metabolic function. This disruption involves pathways controlling cellular homeostasis as well as metabolically-driven chronic inflammatory states. Hence, an understanding of these relationships would help improve treatments and, as well, identify new therapeutic targets.

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Fibroblast growth factor 1 ameliorates adipose tissue inflammation and systemic insulin resistance via enhancing adipocyte mTORC2/Rictor signal

Abstract: This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Cited by 12 publications

References 43 publications

New developments in the biology of fibroblast growth factors

New developments in the biology of fibroblast growth factors

Loss of CTRP10 results in female obesity with preserved metabolic health

On the Role of Paraoxonase-1 and Chemokine Ligand 2 (C-C motif) in Metabolic Alterations Linked to Inflammation and Disease. A 2021 Update

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