# Impact of SGLT-2 Inhibition on the Cardiometabolic Profile of PCOS

> **NIH NIH F30** · UNIVERSITY OF MISSISSIPPI MED CTR · 2022 · $38,607

## Abstract

Polycystic Ovary Syndrome (PCOS) is the most common endocrine disorder affecting women of reproductive
age, afflicting between 5-20% of women worldwide. It is characterized by hyperandrogenemia and oligo-
ovulation. PCOS is highly co-prevalent with several cardiovascular risk factors such as obesity, hypertension,
insulin resistance, and dyslipidemia. Mitochondrial dysfunction in women with PCOS is also apparent which
could lead to the unhealthy expansion of white adipose tissue (WAT) seen in PCOS. While the exact etiology
of PCOS is unknown, hyperandrogenemia appears to be a major mediator of the cardiometabolic profile of
PCOS. With these knowledge gaps, it is unsurprising that there are limited options for women with PCOS to
reduce their cardiovascular risk factors. As cardiovascular disease is the number one killer of women in the
United States, women with PCOS desperately need more treatment options. Treatments such as metformin
and angiotensin II receptor blockers have shown some promise, but they only treat part of the disease. Among
these new potential treatments are sodium-glucose co-transporter 2 inhibitors (SGLT2i), an exciting class of
therapeutic tools that reduces BP and cardiovascular mortality in patients with type 2 diabetes. Recently,
SGLT2i reduced the body weight of women with PCOS. Additionally, in mice with insulin resistance, SGLT2i
increased markers of fatty acid oxidation and decreased urinary 8-isoprostane, a marker of oxidative stress.
Therefore, SGLT2i need to be investigated for treatment of PCOS as they may reduce obesity, BP,
dyslipidemia, and renal injury in this disease. To study SGLT2i in PCOS, our laboratory has previously
characterized a Sprague Dawley female rat model of PCOS via implantation of a dihydrotestosterone pellet at
four weeks of age. Our hyperandrogenemic female (HAF) rats mimic many of the same features of PCOS
women such as oligo-ovulation accompanied by increased adiposity, BP, insulin resistance, and renal injury.
We have exciting preliminary data that SGLT2i decreases adiposity in our model, with evidence of functional
improvement of WAT from a marked decreased in plasma leptin. We also found reduced expression of renal
angiotensin-converting enzyme mRNA. This project will test the central hypothesis that pharmacological
administration of SGLT2i in HAF rats will ameliorate both the increase in BP by downregulating the intrarenal
renin-angiotensin system (RAS) and obesity by improving mitochondrial function in WAT. This hypothesis will
be tested in the following specific aims: 1) To test the hypothesis that in HAF rats, androgens increase SGLT2
that leads to activation of the RAS leading to increased BP and reduced renal function, and administration of
an SGLT2i will decrease BP and improve renal hemodynamics, and 2) To test the hypothesis that in HAF rats,
androgens cause mitochondrial dysfunction in WAT and that SGLT2i will attenuate androgen-induced
mitochondrial dysfunction leading to impro...

## Key facts

- **NIH application ID:** 10355464
- **Project number:** 5F30DK127527-02
- **Recipient organization:** UNIVERSITY OF MISSISSIPPI MED CTR
- **Principal Investigator:** Jacob E Pruett
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $38,607
- **Award type:** 5
- **Project period:** 2021-03-01 → 2023-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10355464

## Citation

> US National Institutes of Health, RePORTER application 10355464, Impact of SGLT-2 Inhibition on the Cardiometabolic Profile of PCOS (5F30DK127527-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10355464. Licensed CC0.

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