Role of PTP1B in POMC neurons during chronic high-fat diet: sex differences in regulation of liver lipids and glucose tolerance
Open accessAbstract
Protein tyrosine phosphatase 1B (PTP1B) is a negative regulator of leptin receptor signaling and may contribute to leptin resistance in diet-induced obesity. Although PTP1B inhibition has been suggested as a potential weight loss therapy, the role of specific neuronal PTP1B signaling in cardiovascular and metabolic regulation and the importance of sex differences in this regulation are still unclear. In this study, we investigated the impact of proopiomelanocortin (POMC) neuronal PTP1B deficiency in cardiometabolic regulation in male and female mice fed a high-fat diet (HFD). When compared with control mice (PTP1B flox/flox), male and female mice deficient in POMC neuronal PTP1B (PTP1B flox/flox/POMC-Cre) had attenuated body weight gain (males: −18%; females: −16%) and fat mass (males: −33%; female: −29%) in response to HFD. Glucose tolerance was improved by 40%, and liver lipid accumulation was reduced by 40% in PTP1B/POMC-Cre males but not in females. When compared with control mice, deficiency of POMC neuronal PTP1B did not alter mean arterial pressure (MAP) in male or female mice (males: 112 ± 1 vs. 112 ± 1 mmHg in controls; females: 106 ± 3 vs. 109 ± 3 mmHg in controls). Deficiency of POMC neuronal PTP1B also did not alter MAP response to acute stress in males or females compared with control mice (males: Δ32 ± 0 vs. Δ29 ± 4 mmHg; females: Δ22 ± 2 vs. Δ27 ± 4 mmHg). These data demonstrate that POMC-specific PTP1B deficiency improved glucose tolerance and attenuated diet-induced fatty liver only in male mice and attenuated weight gain in males and females but did not enhance the MAP and HR responses to a HFD or to acute stress.
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POMC-specific PTP1B deficiency did not enhance blood pressure and heart rate responses to hyperleptinaemia induced by a high-fat diet but did improve glucose tolerance in male mice.
“Surprisingly, POMC-specific PTP1B deficiency did not enhance BP and HR responses to hyperleptinaemia induced by an HFD but did improve glucose tolerance in male mice149.”
From Obesity, kidney dysfunction and hypertension: mechanistic links (2019) · cites this paper as [149]
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- Authors
- Aberdein, N., Dambrino, R. J., do Carmo, J. M., Wang, Z., Mitchell, L. E., Drummond, H. A., & Hall, J. E.
- Affiliations
- University of Mississippi Medical Center (US)
- Department of Physiology and Biophysics, Mississippi Center for Obesity Research, University of Mississippi Medical Center, Jackson, Mississippi
- Corresponding author
- Aberdein, Nicola
- Venue
- American Journal of Physiology-Regulatory, Integrative and Comparative Physiology
- Publisher
- American Physiological Society
- Published
- 2018-03-01
- Volume
- 314
- Issue
- 3
- Pages
- R478-R488
- ISSN
- 0363-6119 (ISSN-L)
- 1522-1490
- PMC
- PMC5899251
- OpenAlex
- W2777176056
- Cited by
- 21
- References
- 31
- Citations by year
- 2026: 2 · 2024: 4 · 2023: 2 · 2022: 4 · 2021: 1 · 2020: 3 · 2019: 5
- FWCI
- 1.25
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- American Journal of Physiology-Regulatory, Integrative and Comparative Physiology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- SHURA (Sheffield Hallam University Research Archive) (Sheffield Hallam University) (acceptedVersion)
- Funders
- HHS | NIH | National Heart, Lung, and Blood Institute (NHBLI) (P01 HL51971)
- HHS | NIH | National Institute of General Medical Sciences (NIGMS) (P20 GM104357, U54 GM115428)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Tyrosine Phosphatases
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Keywords
- PTP1B, proopiomelanocortin neurons, leptin resistance, leptin receptor signaling, high-fat diet, diet-induced obesity, sex differences, glucose tolerance, hepatic lipid accumulation, hepatic steatosis, weight gain, fat mass, mean arterial pressure, acute stress response, heart rate
- MeSH terms
- Animals, Arcuate Nucleus of Hypothalamus, Blood Glucose, Disease Models, Animal, Female, Liver, Male, Mice, Inbred C57BL, Neurons, Obesity, Pro-Opiomelanocortin, Sex Factors, Biomarkers, Weight Gain, Solitary Nucleus, Glucose Intolerance, Mice, Knockout, Lipid Metabolism, Protein Tyrosine Phosphatase, Non-Receptor Type 1, Mice, 129 Strain, Diet, High-Fat, Non-alcoholic Fatty Liver Disease
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