Increased energy expenditure, decreased adiposity, and tissue-specific insulin sensitivity in protein-tyrosine phosphatase 1B-deficient mice
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Published on: November 27, 2019
L D Klaman1, O Boss, O D Peroni
1Cancer Biology Program, Division of Hematology-Oncology, Boston, Massachusetts 02215, USA.
Abstract:
Protein-tyrosine phosphatase 1B (PTP-1B) is a major protein-tyrosine phosphatase that has been implicated in the regulation of insulin action, as well as in other signal transduction pathways. To investigate the role of PTP-1B in vivo, we generated homozygotic PTP-1B-null mice by targeted gene disruption. PTP-1B-deficient mice have remarkably low adiposity and are protected from diet-induced obesity. Decreased adiposity is due to a marked reduction in fat cell mass without a decrease in adipocyte number. Leanness in PTP-1B-deficient mice is accompanied by increased basal metabolic rate and total energy expenditure, without marked alteration of uncoupling protein mRNA expression. In addition, insulin-stimulated whole-body glucose disposal is enhanced significantly in PTP-1B-deficient animals, as shown by hyperinsulinemic-euglycemic clamp studies. Remarkably, increased insulin sensitivity in PTP-1B-deficient mice is tissue specific, as insulin-stimulated glucose uptake is elevated in skeletal muscle, whereas adipose tissue is unaffected. Our results identify PTP-1B as a major regulator of energy balance, insulin sensitivity, and body fat stores in vivo.
Insights
Removing Protein-tyrosine phosphatase 1B (PTP-1B) reduces body fat and protects against obesity. PTP-1B deficiency enhances insulin sensitivity, particularly in skeletal muscle, improving glucose disposal and energy balance.
Area of Science:
- Biochemistry
- Metabolic Research
- Genetics
Background:
- Protein-tyrosine phosphatase 1B (PTP-1B) plays a role in insulin signaling.
- Dysregulation of PTP-1B is linked to metabolic disorders.
Purpose of the Study:
- To investigate the in vivo function of PTP-1B.
- To determine the role of PTP-1B in regulating energy balance and insulin sensitivity.
Main Methods:
- Generation of homozygotic PTP-1B-null mice via gene targeting.
- Assessment of adiposity, metabolic rate, and energy expenditure.
- Hyperinsulinemic-euglycemic clamp studies to evaluate glucose disposal.
Main Results:
- PTP-1B-deficient mice exhibit significantly reduced adiposity and protection from diet-induced obesity.
- Leanness correlates with increased basal metabolic rate and total energy expenditure.
- Enhanced insulin-stimulated glucose uptake in skeletal muscle, but not adipose tissue, leading to improved whole-body glucose disposal.
Conclusions:
- PTP-1B is a critical regulator of body fat stores and energy homeostasis in vivo.
- Targeting PTP-1B may offer a therapeutic strategy for obesity and insulin resistance.
- Tissue-specific effects of PTP-1B deficiency on insulin sensitivity highlight its complex role in metabolic regulation.
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