Depletion of regulator-of-G-protein signaling-10 in mice exaggerates high-fat diet-induced insulin resistance and inflammation, and this effect is mitigated by dietary green tea extract

Fang, Xi; Chung, Julianne; Olsén, Erik; Snider, Isabelle; Earls, Rachael H.; Jeon, Julie; Park, Hea Jin; Lee, Jae‐Kyung

doi:10.1016/j.nutres.2018.06.004

Cited by 8 publications

(11 citation statements)

References 64 publications

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“…External KOs for the neuronal calcium sensor Ncs1 and the GTPase-activating protein Rgs10 were obese, 142 , 143 consistent with our findings ( Table 3 ). Although no publications link the P2RX6 channel 144 to obesity, the IMPC HTS found that male P2rx6 KO mice were obese; the obesity observed in our P2rx6 KO mice ( Table 3 ) was present in both males and females (data not shown).…”

Section: Resultssupporting

confidence: 89%

High-Throughput Screening of Mouse Gene Knockouts Identifies Established and Novel High Body Fat Phenotypes

Powell¹,

Revelli²,

Doree³

et al. 2021

DMSO

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Purpose Obesity is a major public health problem. Understanding which genes contribute to obesity may better predict individual risk and allow development of new therapies. Because obesity of a mouse gene knockout (KO) line predicts an association of the orthologous human gene with obesity, we reviewed data from the Lexicon Genome5000 TM high throughput phenotypic screen (HTS) of mouse gene KOs to identify KO lines with high body fat. Materials and Methods KO lines were generated using homologous recombination or gene trapping technologies. HTS body composition analyses were performed on adult wild-type and homozygous KO littermate mice from 3758 druggable mouse genes having a human ortholog. Body composition was measured by either DXA or QMR on chow-fed cohorts from all 3758 KO lines and was measured by QMR on independent high fat diet-fed cohorts from 2488 of these KO lines. Where possible, comparisons were made to HTS data from the International Mouse Phenotyping Consortium (IMPC). Results Body fat data are presented for 75 KO lines. Of 46 KO lines where independent external published and/or IMPC KO lines are reported as obese, 43 had increased body fat. For the remaining 29 novel high body fat KO lines, Ksr2 and G2e3 are supported by data from additional independent KO cohorts, 6 ( Asnsd1, Srpk2, Dpp8, Cxxc4, Tenm3 and Kiss1 ) are supported by data from additional internal cohorts, and the remaining 21 including Tle4, Ak5, Ntm, Tusc3, Ankk1, Mfap3l, Prok2 and Prokr2 were studied with HTS cohorts only. Conclusion These data support the finding of high body fat in 43 independent external published and/or IMPC KO lines. A novel obese phenotype was identified in 29 additional KO lines, with 27 still lacking the external confirmation now provided for Ksr2 and G2e3 KO mice. Undoubtedly, many mammalian obesity genes remain to be identified and characterized.

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Section: Resultssupporting

confidence: 89%

High-Throughput Screening of Mouse Gene Knockouts Identifies Established and Novel High Body Fat Phenotypes

Powell¹,

Revelli²,

Doree³

et al. 2021

DMSO

View full text Add to dashboard Cite

show abstract

“…In comparison to WT, HFD-fed RGS10-deficient mice are more susceptible to the body weight gain associated with larger white adipose and liver tissue masses. More importantly, HFD-fed RGS10-deficient mice exhibit insulin resistance, while glucose intolerance and higher leptin levels are observed in RGS10-deficient mice following either LFD or HFD feeding compared to WT mice [131]. Furthermore, since RGS10 serves as an anti-inflammatory protein in macrophage activation, RGS10-deficient mice fed with HFD are more susceptible to chronic inflammation, as evidenced by higher M1 inflammatory gene transcripts in the liver and adipose tissues and lower mRNAs of Fizz1 and YM1 anti-inflammatory M2 markers [131].…”

Section: Metabolic Disordersmentioning

confidence: 95%

“…More importantly, HFD-fed RGS10-deficient mice exhibit insulin resistance, while glucose intolerance and higher leptin levels are observed in RGS10-deficient mice following either LFD or HFD feeding compared to WT mice [131]. Furthermore, since RGS10 serves as an anti-inflammatory protein in macrophage activation, RGS10-deficient mice fed with HFD are more susceptible to chronic inflammation, as evidenced by higher M1 inflammatory gene transcripts in the liver and adipose tissues and lower mRNAs of Fizz1 and YM1 anti-inflammatory M2 markers [131]. Thus, this study sheds light on the importance of RGS10 in managing HFD-induced body weight gain and related metabolic disorders.…”

Section: Metabolic Disordersmentioning

confidence: 95%

“…A high-fat diet (HFD), as one of the highly impactful environmental factors, induces body weight gain and central obesity, with various metabolic abnormalities. The role of RGS10 in metabolic changes related to HFD consumption has been studied in mice, where RGS10 expression is downregulated in the liver and upregulated in adipose tissues of WT mice fed with HFD compared to low-fat diet (LFD)-fed mice [131]. In comparison to WT, HFD-fed RGS10-deficient mice are more susceptible to the body weight gain associated with larger white adipose and liver tissue masses.…”

Section: Metabolic Disordersmentioning

confidence: 99%

“…BMDM, bone marrow derived macrophage; FSL-1, Pam2CGDPKHPKSF, synthetic diacylated lipoprotein; LPS, lipopolysaccharide; MN9D, mesencephalon neuroblastoma cell line; RANKL, receptor activator of nuclear factor-κB-ligand; TNF-α, tumor necrosis factor-alpha; TSA, trichostatin A; 5-Aza, 5-Azacytidine; M-CSF, Macrophage colony-stimulating factor; S1P, sphingosine-1-phosphate; pSNL, partial sciatic nerve ligation. [47,111] Neuroinflammation and neurodegeneration Parkinson's disease and a possible link to schizophrenia 2008 [48,94,96] Reduced chemotherapy-induced cell death Ovarian cancer chemoresistance 2010 [124,125] Hypertrophy following pressure overload Heart failure 2015 [108] Platelets aggregation and thrombogenesis Aspirin resistance 2016 [119,121] Increased body weight with insulin resistance and glucose intolerance Obesity and related metabolic syndromes 2019 [131] Cell Signal. Author manuscript; available in PMC 2021 November 01.…”

Section: -Conclusion and Future Perspectivementioning

confidence: 99%

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Regulator of G protein signaling 10: Structure, expression and functions in cellular physiology and diseases

Almutairi

Lee

Rada

2020

Cellular Signalling

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Regulator of G‐protein signaling 14 protects the liver from ischemia–reperfusion injury by suppressing TGF‐β‐activated kinase 1 activation

et al. 2021

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Background and Aims: Hepatic ischemia-reperfusion injury (IRI) is a common complication of hepatectomy and liver transplantation. However, the mechanisms underlying hepatic IRI have not been fully elucidated. Regulator of G-protein signaling 14 (RGS14) is a multifunctional scaffolding protein that integrates the G-protein and mitogen-activated protein kinase (MAPK) signaling pathways. However, the role of RGS14 in hepatic IRI remains unclear. Approach and Results:We found that RGS14 expression increased in mice subjected to hepatic ischemia-reperfusion (IR) surgery and during hypoxia reoxygenation in hepatocytes. We constructed global RGS14 knockout (RGS14-KO) and hepatocyte-specific RGS14 transgenic (RGS14-TG) mice to establish 70% hepatic IRI models. Histological hematoxylin and eosin staining, levels of alanine aminotransferase and aspartate aminotransferase, expression of inflammatory factors, and apoptosis were used to assess liver damage and function in these models. We found that RGS14 deficiency significantly aggravated IR-induced liver injury and activated hepatic inflammatory responses and apoptosis in vivo and in vitro. Conversely, RGS14 overexpression exerted the opposite effect of the RGS14-deficient models. Phosphorylation of TGFβ-activated kinase 1 (TAK1) and its downstream effectors c-Jun N-terminal kinase (JNK) and p38 increased in the

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Depletion of regulator-of-G-protein signaling-10 in mice exaggerates high-fat diet-induced insulin resistance and inflammation, and this effect is mitigated by dietary green tea extract

Cited by 8 publications

References 64 publications

High-Throughput Screening of Mouse Gene Knockouts Identifies Established and Novel High Body Fat Phenotypes

High-Throughput Screening of Mouse Gene Knockouts Identifies Established and Novel High Body Fat Phenotypes

Regulator of G protein signaling 10: Structure, expression and functions in cellular physiology and diseases

Regulator of G‐protein signaling 14 protects the liver from ischemia–reperfusion injury by suppressing TGF‐β‐activated kinase 1 activation

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