The Genetics of<i>PTPN1</i>and Obesity: Insights from Mouse Models of Tissue-Specific PTP1B Deficiency

Tsou, Ryan C.; Bence, Kendra K.

doi:10.1155/2012/926857

Cited by 39 publications

(29 citation statements)

References 61 publications

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“…In F0, we saw a significant increase only in the expression of mRNA levels of Pdk4 , a mitochondrial enzyme that is a key negative regulator of glucose oxidation (19). In F1, the mRNA levels for Pdk4, H19 , and Ptpn1 , a negative regulator of both insulin and leptin signaling involved in the control of glucose homeostasis and EE (21), were all reduced, whereas the mRNA for Slc2a4 , a glucose transporter protein, was increased in EFO compared with thatin CFO muscle ( Fig . 5 ).…”

Section: Resultsmentioning

confidence: 99%

“…6 ). Genes with significant methylation changes included Ogt and Oga (enzymes involved in cycling of O ‐GlcNAc), 2 genes that are known to negatively influence insulin sensitivity in muscle cells and adipocytes by inhibiting phosphorylation of Akt1 (22); H19 , an imprinted gene that is involved in the negative regulation of body weight (20); and Ptpn1 (Ptp1B), a negative regulator of the insulin signaling pathway (21). We further examined the methylation pattern of the same promoter regions in offspring sperm after 12 wk on the control diet.…”

Section: Resultsmentioning

confidence: 99%

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Paternal long‐term exercise programs offspring for low energy expenditure and increased risk for obesity in mice

et al. 2015

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Obesity has more than doubled in children and tripled in adolescents in the past 30 yr. The association between metabolic disorders in offspring of obese mothers with diabetes has long been known; however, a growing body of research indicates that fathers play a significant role through presently unknown mechanisms. Recent observations have shown that changes in paternal diet may result in transgenerational inheritance of the insulin-resistant phenotype. Although diet-induced epigenetic reprogramming via paternal lineage has recently received much attention in the literature, the effect of paternal physical activity on offspring metabolism has not been adequately addressed. In the current study, we investigated the effects of long-term voluntary wheel-running in C57BL/6J male mice on their offspring's predisposition to insulin resistance. Our observations revealed that fathers subjected to wheel-running for 12 wk produced offspring that were more susceptible to the adverse effects of a high-fat diet, manifested in increased body weight and adiposity, impaired glucose tolerance, and elevated insulin levels. Long-term paternal exercise also altered expression of several metabolic genes, including Ogt, Oga, Pdk4, H19, Glut4, and Ptpn1, in offspring skeletal muscle. Finally, prolonged exercise affected gene methylation patterns and micro-RNA content in the sperm of fathers, providing a potential mechanism for the transgenerational inheritance. These findings suggest that paternal exercise produces offspring with a thrifty phenotype, potentially via miRNA-induced modification of sperm.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Paternal long‐term exercise programs offspring for low energy expenditure and increased risk for obesity in mice

et al. 2015

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“…PTP1B 2 is implicated in regulation of energy balance; single nucleotide polymorphisms within the human PTPN1 gene are associated with obesity and metabolic disorders (2), and deletion of PTP1B in mice (Ptpn1 Ϫ/Ϫ ) results in reduced adiposity and resistance to dietinduced obesity (3,4).…”

mentioning

confidence: 99%

Protein-tyrosine Phosphatase 1B (PTP1B) Is a Novel Regulator of Central Brain-derived Neurotrophic Factor and Tropomyosin Receptor Kinase B (TrkB) Signaling

Ozek

Kanoski

Zhang

et al. 2014

Journal of Biological Chemistry

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Background:The tropomyosin receptor kinase B (TrkB) is a potential novel substrate of protein-tyrosine phosphatase 1B (PTP1B). Results: PTP1B associates with and plays a modulatory role in BDNF-induced TrkB signaling. Conclusion: PTP1B is a novel negative regulator of central BDNF/TrkB signaling. Significance: This is the first evidence that PTP1B deficiency enhances central TrkB signaling and alters BDNF-induced thermogenesis in vivo.

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“…An interesting paradox to the beneficial role of these regulatory phosphates is that both MKP-1 and PTP1b have negative effects on metabolic function [57, 58]. In this regard, global knockdown of these phosphatases improves insulin-sensitivity and prevents diet-induced obesity [59, 60].…”

Section: Ros and Redox-signaling In The Brain: Influences On Bloodmentioning

confidence: 99%

The Brain Renin-Angiotensin System and Mitochondrial Function: Influence on Blood Pressure and Baroreflex in Transgenic Rat Strains

Nautiyal

Arnold

Chappell

et al. 2013

International Journal of Hypertension

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Mitochondrial dysfunction is implicated in many cardiovascular diseases, including hypertension, and may be associated with an overactive renin-angiotensin system (RAS). Angiotensin (Ang) II, a potent vasoconstrictor hormone of the RAS, also impairs baroreflex and mitochondrial function. Most deleterious cardiovascular actions of Ang II are thought to be mediated by NADPH-oxidase- (NOX-) derived reactive oxygen species (ROS) that may also stimulate mitochondrial oxidant release and alter redox-sensitive signaling pathways in the brain. Within the RAS, the actions of Ang II are counterbalanced by Ang-(1–7), a vasodilatory peptide known to mitigate against increased oxidant stress. A balance between Ang II and Ang-(1–7) within the brain dorsal medulla contributes to maintenance of normal blood pressure and proper functioning of the arterial baroreceptor reflex for control of heart rate. We propose that Ang-(1–7) may negatively regulate the redox signaling pathways activated by Ang II to maintain normal blood pressure, baroreflex, and mitochondrial function through attenuating ROS (NOX-generated and/or mitochondrial).

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The Genetics ofPTPN1and Obesity: Insights from Mouse Models of Tissue-Specific PTP1B Deficiency

Cited by 39 publications

References 61 publications

Paternal long‐term exercise programs offspring for low energy expenditure and increased risk for obesity in mice

Paternal long‐term exercise programs offspring for low energy expenditure and increased risk for obesity in mice

Protein-tyrosine Phosphatase 1B (PTP1B) Is a Novel Regulator of Central Brain-derived Neurotrophic Factor and Tropomyosin Receptor Kinase B (TrkB) Signaling

The Brain Renin-Angiotensin System and Mitochondrial Function: Influence on Blood Pressure and Baroreflex in Transgenic Rat Strains

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