Arginylation regulates adipogenesis by regulating expression of PPARγ at transcript and protein level

Singh, Archana; Borah, Anuj Kumar; Deka, Kamalakshi; Gogoi, Akash Protim; Verma, Kamalesh; Barah, Pankaj; Saha, Swati

doi:10.1016/j.bbalip.2018.12.015

Cited by 10 publications

(6 citation statements)

References 54 publications

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“…A 366.3-kb copy-gain CNV encompassing FGFR2 and ATE1 was identified in a proband also deficient for BBS5 (Table 1). ATE1 is reported to affect adipogenesis and adipocyte function (19). Another 858-kb copy-gain CNV affecting the LIPI gene, which is involved in regulation of fat metabolism (20), was identified in a severely obese proband (Table 2).…”

Section: Variants Of Uncertain Significance: Point Mutations In Obesity Genesmentioning

confidence: 99%

Genetic Causes of Severe Childhood Obesity: A Remarkably High Prevalence in an Inbred Population of Pakistan

et al. 2020

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Monogenic forms of obesity have been identified in ≤10% of severely obese European patients. However, the overall spectrum of deleterious variants (point mutations and structural variants) responsible for childhood severe obesity remains elusive. In this study, we genetically screened 225 severely obese children from consanguineous Pakistani families through a combination of techniques, including an in-house–developed augmented whole-exome sequencing method (CoDE-seq) that enables simultaneous detection of whole-exome copy number variations (CNVs) and point mutations in coding regions. We identified 110 (49%) probands carrying 55 different pathogenic point mutations and CNVs in 13 genes/loci responsible for nonsyndromic and syndromic monofactorial obesity. CoDE-seq also identified 28 rare or novel CNVs associated with intellectual disability in 22 additional obese subjects (10%). Additionally, we highlight variants in candidate genes for obesity warranting further investigation. Altogether, 59% of cases in the studied cohort are likely to have a discrete genetic cause, with 13% of these as a result of CNVs, demonstrating a remarkably higher prevalence of monofactorial obesity than hitherto reported and a plausible overlapping of obesity and intellectual disabilities in several cases. Finally, inbred populations with a high prevalence of obesity provide unique, genetically enriched material in the quest of new genes/variants influencing energy balance.

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Section: Variants Of Uncertain Significance: Point Mutations In Obesity Genesmentioning

confidence: 99%

Genetic Causes of Severe Childhood Obesity: A Remarkably High Prevalence in an Inbred Population of Pakistan

et al. 2020

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“…Peroxisome proliferator-activated receptors (PPARs) are ligand-activated nuclear hormone receptor superfamily transcription factors, consisting of three members, PPARα, PPARγ and PPARδ. Previous studies showed that PPARγ participates in many biological processes, such as adipogenesis, energy metabolism and cellular proliferation (4,5). PPARγ coactivator-1α (PGC-1α) forms a complex with PPARγ, coactivates multiple transcription factors and coordinately governs transcriptional control of several metabolic processes (6).…”

Section: Introductionmentioning

confidence: 99%

“…PPARγ coactivator-1α (PGC-1α) forms a complex with PPARγ, coactivates multiple transcription factors and coordinately governs transcriptional control of several metabolic processes (6). PPARγ downregulation has been found to be associated with pathogenesis of various CVDs, including HF (4,5). PPARγ activation increases glucose and free fatty acid uptake and glycerol lipid biosynthesis (7)(8)(9).…”

Section: Introductionmentioning

confidence: 99%

Citri Reticulatae Pericarpium protects against isoproterenol-induced chronic heart failure via activation of PPARγ

Cheng¹,

Wu²,

Ni³

et al. 2020

Ann Transl Med

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Background: Accumulated clinical trials and animal studies showed that Qiliqiangxin (QLQX), a traditional Chinese medicine formula containing extracts of 11 herbs, exerts beneficial effects on chronic heart failure (HF). Citri Reticulatae Pericarpium (CRP), one herbal medicine in QLQX, has been widely used in treatment against digestive, respiratory and cardiovascular diseases (CVDs) in China. However, the cardiac protective effects and mechanisms of CRP are still unclear.Methods: The effects of CRP were investigated in isoproterenol (ISO)-induced chronic HF mice model and neonatal rat ventricular cardiomyocytes (NRVMs) treated with ISO. Echocardiography was used to determine cardiac function. Hematoxylin-eosin (HE) staining and α-actinin immunofluorescent staining were used to measure cardiomyocyte size. Cardiac fibrosis was evaluated by Masson's trichrome staining.The expression of atrial natriuretic polypeptide (ANP) and brain natriuretic polypeptide (BNP) were determined by quantitative real time PCR (qRT-PCR). Western blot was applied to examine the expression of peroxisome proliferator-activated receptor gamma (PPARγ), PPARγ coactivator-1α (PGC-1α), fibrosisrelated and apoptosis-related proteins.Results: We found that CRP could significantly attenuate ISO-induced cardiac dysfunction, inhibit cardiac pathological hypertrophy and alleviate myocardial fibrosis and apoptosis. Mechanistically, the downregulation of PPARγ and PGC-1α in ISO-injected mice hearts and ISO-treated NRVMs could be reversed by CRP treatment. The beneficial effects of CRP against ISO-induced HF were abolished by PPARγ inhibitor (T0070907), suggesting that CRP-mediated PPARγ upregulation was essential for the preventive effect of CRP on ISO-induced cardiac dysfunction. Conclusions:In conclusion, our study demonstrated that CRP attenuates ISO-induced cardiac remodeling via PPARγ activation, which represents a new application for CRP in the prevention of chronic HF.

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“…When confluency of the cells reached approximately 70%, the cells were exposed to different doses of the extract CRACE for 24 h or 48 h; subsequently, and cell survivability was measured by MTT (Sigma M2128) assay following standard procedure [16, 17]. 3T3-L1 cells were differentiated following previously reported method with minor modifications [18, 19]. Briefly, 3T3-L1 cells were seeded (3 X 10 5 cells/well of a 35 mm dish) in maintenance medium and allowed to grow till 100% confluency.…”

Section: Methodsmentioning

confidence: 99%

“…Accumulated intracellular lipid was stained with Oil Red O (ORO) as described before with few modifications [19]. Briefly, cells were stained with 3:2 of 0.3% ORO in isopropanol and water for 5–10 min followed by three 60% isopropanol washes, and three water washes.…”

Section: Methodsmentioning

confidence: 99%

1α, 25-dihydroxy Vitamin D3 containing fractions of Catharanthus roseus leaf aqueous extract inhibit preadipocyte differentiation and induce lipolysis in 3T3-L1 cells

Borah

Singh

Yasmin

et al. 2019

BMC Complement Altern Med

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BackgroundTo investigate the potential of Catharanthus roseus leaf aqueous crude extract (CRACE) as a regulator of adipocyte development and function.Methods3T3-L1 adipogenesis model was used to investigate the effect of CRACE on adipogenesis. 3T3-L1 preadipocytes (for adipogenic differentiation) and mature 3T3-L1 adipocytes (for adipocyte function) were treated with non-toxic doses of CRACE. The outcomes were corroborated by intracellular lipid accumulation, expression of pro-and anti-adipogenic effector molecules. To investigate CRACE mediated lipolysis, cAMP accumulation, glycerol release and phosphorylation of key effector molecules were tested in treated mature adipocytes. Finally, the extract was fractionated to identify the active molecule/s in the extract.ResultsCRACE significantly reduced adipocyte differentiation by modulating PPARγ expression. At early stage CRACE directly targeted Lipin1 expression and consequently impacted KLF7, subsequently expression of GATA2, CEBPα, SREBP1c were targeted, with PPARγ expression, particularly curtailed. While CRACE significantly reduced several lipogenic genes like FAS and GPD1 in mature adipocytes, concomitantly, it greatly increased lipolysis resulting in decreased lipid accumulation in mature adipocytes. The increase in lipolysis was due to decreased Akt activation, increased cAMP level, and PKA activity. The fractionation of CRACE allowed identification of two fractions with potent anti-adipogenic activity. Both the fractions contained 1α, 25-dihydroxy Vitamin D3 as major component.Conclusions1α, 25-dihydroxy Vitamin D3 containing CRACE can be developed into an effective anti-obesity formulation that decreases adipogenesis and increases lipid catabolism.

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Arginylation regulates adipogenesis by regulating expression of PPARγ at transcript and protein level

Cited by 10 publications

References 54 publications

Genetic Causes of Severe Childhood Obesity: A Remarkably High Prevalence in an Inbred Population of Pakistan

Genetic Causes of Severe Childhood Obesity: A Remarkably High Prevalence in an Inbred Population of Pakistan

Citri Reticulatae Pericarpium protects against isoproterenol-induced chronic heart failure via activation of PPARγ

1α, 25-dihydroxy Vitamin D3 containing fractions of Catharanthus roseus leaf aqueous extract inhibit preadipocyte differentiation and induce lipolysis in 3T3-L1 cells

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