PARP1 deficiency exacerbates diet-induced obesity in mice

Devalaraja-Narashimha, Kishor; Padanilam, Babu J.

doi:10.1677/joe-09-0402

Cited by 59 publications

(48 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…PARP deletion probably exerts both positive and negative effects. A previous study demonstrated that PARP1 deficiency promotes the lipid accumulation in liver [12] and exacerbates high-fat diet-induced obesity [6]. In the present study, shortterm PARP inhibition also enhanced the lipid synthesis in the liver tissues of mice fed with a high-fat diet, indicating that PARP is involved in the lipid metabolism via gene modulation.…”

Section: Discussionsupporting

confidence: 74%

See 1 more Smart Citation

Inhibition of Poly(ADP-Ribose) Polymerase Increased Lipid Accumulation Through SREBP1 Modulation

Pang

Chen

et al. 2018

Cell Physiol Biochem

View full text Add to dashboard Cite

Background/Aims: Excess energy intake leads to metabolic dysfunction, accompanied by oxidative stress and poly(ADP-ribose) polymerase (PARP) activation. Methods: To determine the role of PARP activation in the incidence of metabolic dysfunction, PJ34, the PARP inhibitor, was administered to the oleic acid-treated hepatoma cells and high-fat diet-fed mice. The expression of genes was detected by quantitative real-time PCR and western blotting. Lipid droplets in the cells and tissues were stained with Oil Red O. Results: PJ34 treatment aggravated oleic acid-induced lipid accumulation in hepatoma cells and induced SREBP1 expression by modulating the modification of transcription factor specificity protein 1 (Sp1). The high-fat diet-mice exhibited hyperglycemia, insulin resistance and lipid accumulation after 3 months of feeding. Although the serum level of lipid was not altered after PJ34 treatment, the expression level of lipogenic gene was up-regulated and the lipid accumulation was increased in the liver tissues of high-fat diet + PJ34-treated mice. In the high-fat diet + PJ34-treated mice, the insulin sensitivity was slightly changed and the levels of blood glucose and serum insulin were decreased compared with the mice fed with a high-fat diet alone. Conclusion: Taken together, PARP inhibition up-regulated the expression level of lipogenic gene and significantly induced lipid accumulation in the liver, which might worsen lipid metabolism disorders. These data will guide future research into the application of PARP inhibitors in the management of metabolic diseases.

show abstract

Section: Discussionsupporting

confidence: 74%

“…PARP1 gene deletion has been reported to enhance the lipid accumulation in liver and exacerbate high fat-induced obesity [6]. The beneficial function of PARP may be impaired when the PARP1 gene is deleted.…”

Section: Original Papermentioning

confidence: 99%

Inhibition of Poly(ADP-Ribose) Polymerase Increased Lipid Accumulation Through SREBP1 Modulation

Pang

Chen

et al. 2018

Cell Physiol Biochem

View full text Add to dashboard Cite

show abstract

“…Recent studies suggest that PARP knockout mice are highly susceptible to diet-induced obesity. 58 Compared to their wild-type counterparts, PARP knockout mice display fat accumulation, hyperleptinemia, insulin resistance, and glucose intolerance; this weight gain is due in part to decreased metabolic rate and total energy expenditure. 58 These findings argue for an important role of the PARP pathway in obesity.…”

Section: Potential Therapeutic Role(s) Of Par/parg Manipulationmentioning

confidence: 99%

Review of Poly (ADP-ribose) Polymerase (PARP) Mechanisms of Action and Rationale for Targeting in Cancer and Other Diseases

Morales

Fattah

et al. 2014

Crit Rev Eukaryot Gene Expr

496

346

View full text Add to dashboard Cite

Poly (ADP-ribose) polymerases (PARPs) are a family of related enzymes that share the ability to catalyze the transfer of ADP-ribose to target proteins. PARPs play an important role in various cellular processes, including modulation of chromatin structure, transcription, replication, recombination, and DNA repair. The role of PARP proteins in DNA repair is of particular interest, in view of the finding that certain tumors defective in homologous recombination mechanisms, may rely on PARP-mediated DNA repair for survival, and are sensitive to its inhibition. PARP inhibitors may also increase tumor sensitivity to DNA-damaging agents. Clinical trials of PARP inhibitors are investigating the utility of these approaches in cancer. The hyperactivation of PARP has also been shown to result in a specific programmed cell death pathway involving NAD+/ATP depletion, mu-calpain activation, loss of mitochondrial membrane potential, and the release of apoptosis inducing factor. Hyperactivation of the PARP pathway may be exploited to selectively kill cancer cells. Other PARP forms, including tankyrase 1 (PARP 5a), which plays an important role in enhancing telomere elongation by telomerase, have been found to be potential targets in cancer therapy. The PARP pathway and its inhibition thus offers a number of opportunities for therapeutic intervention in both cancer and other disease states.

show abstract

“…Recent breakthroughs have come from the realization that the biological roles of a stress-sensing protein, such as PARP-1, should be explored in response to stress, not the pathogen-free, fixed-light, low fat diet environments to which typical laboratory mice are exposed (Luo and Kraus, 2012). This realization led to some groundbreaking stress-response studies in mice demonstrating clear roles for PARP-1 and PARP-2 in metabolism (Bai et al, 2011a; Bai et al, 2011b; Devalaraja-Narashimha and Padanilam, 2010), and for PARP-1 in circadian rhythms (Asher et al, 2010). Studies of PARG function in knockout mice have also revealed important insights, such as the catabolism of PAR is essential for life (Cortes et al, 2004; Koh et al, 2004).…”

Section: Recent Advances Future Prospectsmentioning

confidence: 99%

PARPs and ADP-Ribosylation: 50 Years … and Counting

2015

View full text Add to dashboard Cite

Summary Over 50 years ago, the discovery of poly(ADP-ribose) (PAR) set a new field of science in motion - the field of poly(ADP-ribosyl) transferases (PARPs) and ADP-ribosylation. The field is still flourishing today. The diversity of biological processes now known to require PARPs and ADP-ribosylation was practically unimaginable even two decades ago. From an initial focus on DNA damage detection and repair in response to genotoxic stresses, the field has expanded to include the regulation of chromatin structure, gene expression, and RNA processing in a wide range of biological systems, including reproduction, development, aging, stem cells, inflammation, metabolism, and cancer. This special focus issue of Molecular Cell includes a collection of three Reviews, three Perspectives, and a SnapShot, which together summarize the current state of the field and suggest where it may be headed.

show abstract

PARP1 deficiency exacerbates diet-induced obesity in mice

Cited by 59 publications

References 32 publications

Inhibition of Poly(ADP-Ribose) Polymerase Increased Lipid Accumulation Through SREBP1 Modulation

Inhibition of Poly(ADP-Ribose) Polymerase Increased Lipid Accumulation Through SREBP1 Modulation

Review of Poly (ADP-ribose) Polymerase (PARP) Mechanisms of Action and Rationale for Targeting in Cancer and Other Diseases

PARPs and ADP-Ribosylation: 50 Years … and Counting

Contact Info

Product

Resources

About