# WISE II - Obesity and Type-2 Diabetes: Bariatric Surgery Effects on Brain Function

> **NIH NIH R01** · UNIVERSITY OF FLORIDA · 2024 · $660,338

## Abstract

The obesity epidemic is a major public health problem, contributing to various comorbid medical conditions,
including diabetes, cardiovascular disease, and brain disturbances. The proposed project is designed to
delineate mechanisms underlying the effects of severe obesity on brain health and cognition in the context of
bariatric surgery induced weight loss. Besides causing dramatic weight loss in many patients, bariatric surgery
alters systemic metabolic and vascular function, including altering insulin and glucose metabolism. We have
shown cognitive and neurophysiological benefits of bariatric surgery including enhanced cerebral metabolic
and hemodynamic function tied to reductions in A1C and BMI. Improvements in insulin-glucose regulation are
significant factors in brain health. Findings from the parent R01 (WISE-01) support our earlier findings of
improved cognitive function at 3 months and 18 months post-surgery. We further see changes in fMRI
functional connectivity in brain networks known to be critical in cognitive functions and cerebral metabolic
milieu such that reduced BMI and A1C are associated with lower brain inflammatory markers (MRS). We also
showed that markers of brain function and metabolic states prior to bariatric surgery predict BMI and A1C
reductions. Furthermore, white matter integrity prior to surgery is predictive of cognitive improvement post-
surgery. Our past findings provide compelling evidence linking systemic, cerebral metabolic, and brain function
with successful weight loss and diabetes improvements, but several important clinically and scientifically
significant questions remain. The extent to which improvements in cognition and brain function persist over
longer periods is unknown, motivating the proposed investigation’s Aim 1, an additional assessment of these
factors in WISE-01 participants at >36 months after bariatric surgery. There are multiple mechanisms by which
obesity, weight loss, and, specifically bariatric surgery may affect brain and systemic health. Amongst these,
vagus nerve contributions are compelling as the vagus is a major conduit by which information is conveyed
from the gut to and from the brain. The vagus is commonly cut during bariatric surgery and further, stimulation
methods (e.g., transcutaneous vagus nerve stimulation [tVNS]) have promise in affecting physiology relevant
to weight loss impacts on brain and systemic health. Thus, in Aims 2 and 3, we will prospectively assess the
impact of both of these vagus manipulations on brain/cognitive and systemic health post bariatric surgery (pre-
surgery, 3- and 18- months post-surgery). In Aim 2, the effects of cutting and sparing the anterior vagus during
Roux-en-Y gastric bypass (RYGB) will be assessed. In Aim 3, the effects of tVNS starting three months post-
RYGB will be assessed. These three aims will substantially increase our knowledge of longitudinal effects of
bariatric surgery on brain and systemic health as well as the role of the ...

## Key facts

- **NIH application ID:** 10803224
- **Project number:** 2R01DK099334-06A1
- **Recipient organization:** UNIVERSITY OF FLORIDA
- **Principal Investigator:** RONALD A COHEN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $660,338
- **Award type:** 2
- **Project period:** 2014-06-25 → 2028-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10803224

## Citation

> US National Institutes of Health, RePORTER application 10803224, WISE II - Obesity and Type-2 Diabetes: Bariatric Surgery Effects on Brain Function (2R01DK099334-06A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10803224. Licensed CC0.

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