Jessica Hem, BA

She/Her/Hers

Job Title

Research Technician II

Academic Rank

Staff/Research Assistant

Department

Hematology

Authors

Jessica Hem, BA; Benjamin Rolles, MD; Adela Herce, BS; Jonas Jutzi, MD, PhD; Frederike Kramer, PhD; Anna Marneth, PhD; Swarna Bale, PhD; Ann Mullally, MD

Principal Investigator

Ann Mullally, MD

Categories

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Analyzing the impact of an obesity diet on Myeloproliferative Neoplasms using a Jak2V617F-mutant mouse model

Scientific Abstract

Background: Myeloproliferative neoplasms (MPN) are malignant diseases of the blood caused by mutations including Jak2V617F. We hypothesize that obesity worsens MPN phenotypes and outcomes. We studied the effects of an obesity diet on Jak2V617F-mutant mice that model Polycythemia vera as one of the most common diseases of the MPN group.

Methods: Jak2V617F and control mice were fed an obesity diet (60% kcal fat, 7% sucrose) or control diet (10% kcal fat) (n=8 in each group), for 24 weeks. Blood was drawn bi-weekly for CBC analysis. Food and body weight measurements were taken weekly.

Results: There were no significant changes regarding food consumption in all groups. Control mice fed the obesity diet had significantly increased BMI after 24 weeks (p<0.001). There was no significant increase in BMI, HgB, HCT or RBCs for the Jak2V617F mice fed the obesity diet compared to the Jak2V617F mice fed the control diet . Control mice fed the obesity diet showed impaired glucose tolerance while Jak2V617F mice fed the obesity diet did not. Conclusions: The Jak2V617F mice on the obesity diet did not gain weight. We are exploring possible mechanisms for the lack of weight gain including malabsorption and increased energy expenditure.

Lay Abstract

Background: Myeloproliferative neoplasms (MPN) is a blood cancer caused by genetic mutations. One such mutation is the Jak2V617F mutation that leads to an increase in red blood cells. We hypothesized that obesity worsens MPN characteristics and outcomes in patients with the Jak2V617F mutation. Here we studied how an obesity diet affects MPN in mice with the Jak2V617F mutation.

Methods: Mutant and control mice were fed an obesity or control diet for 24 weeks. Blood was drawn bi-weekly for analysis. Food and body weight measurements were taken weekly.

Results: All mice consumed a similar amount of food. Control mice fed the obesity diet gained weight but Jak2V617F mutant mice fed the obesity diet did not. Additionally, we did not see any differences in red blood cell counts in the mutant mice on the obesity diet compared to the control diet. Control mice fed the obesity diet had higher blood sugar compared to mutant mice fed the obesity diet.

Conclusions: The mutant mice on the obesity diet did not gain weight. We are exploring possible reasons for the lack of weight gain including a limited ability to absorb nutrients and increased energy expenditure.

Clinical Implications

The obesity epidemic is one of the largest threats to public health in the United States. We aim to understand why and how obesity impacts MPN in patients with the Jak2V617F mutation in order to create better future treatment options.