# Metabolic and Endocrine Effects of Bariatric Surgery

> **NIH NIH R01** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2021 · $375,242

## Abstract

Project Summary/Abstract
Weight loss (WL) improves obesity-related co-morbidities such as type 2 diabetes mellitus (DM). Unfortunately,
WL through life-style interventions has a high degree of recidivism and the paucity of safe, effective and
affordable pharmacotherapy together with an increase in the prevalence of morbid obesity has led to a rise in
bariatric procedures. Clinical trials in patients with DM show that improvements in glycemia vary between
procedures and occur in the following order: Roux-en-Y gastric bypass (RYGB) > sleeve gastrectomy (SG) >
laparoscopic adjustable gastric banding (LAGB) > medical/life-style therapy. This order mirrors the amount of
WL with each intervention and is a major driver of glycemic improvement. We have shown profound changes
unique to RYGB and SG in levels of hormones that make up the “gut-brain” and “enteroinsular” axes. The
association of some of these hormones with insulin sensitivity (IS) and glycemia independent of WL strongly
suggests that glycemic improvements after surgery occur in part through pathways that are distinct from just
calorie restriction. A new direction of this application builds on our results showing that levels of fibroblast
growth factor 19 (FGF19), a protein secreted by intestinal cells, are increased after RYGB and SG but not after
low calorie diet (LCD). One of the effects of FGF19 is to improve IS, which in rodents occurs via suppression
of agouti-related protein (AgRP) neurons in the hypothalamus. Another finding in rodents is that FGF19
ameliorates activation of the hypothalamic-pituitary-adrenal (HPA) axis, further adding to the growing evidence
that operating on the gut changes brain activity. We have shown that measurement of plasma AgRP reflects
central activity. Thus, in AIM ONE we will explore the “gut-brain-HPA” axis in humans and test the hypothesis
that diet-induced WL causes an increase in plasma AgRP and activation of the HPA axis whereas equivalent
WL after RYGB or SG do not produce such an increase. These findings are of clinical significance as
preventing activation of the HPA axis may control hunger and allow for long-term maintenance of WL. In AIM
TWO we will utilize proteomic analysis to further extend our investigations of WL dependent and independent
mechanisms that may account for differences in metabolic outcomes between LCD, RYGB and SG. A number
of experimental paradigms indicate that protein secreted from the proximal small intestine induces insulin
resistance which provides a possible explanation as to why RYGB, which excludes this segment of the
intestine, produces superior results compared with SG that are independent of WL. In the proposed Aims
subjects will be carefully characterized with frequently sampled intravenous glucose tolerance tests and mixed
meal tolerance tests. We expect results that will tease out mechanisms related to improvements in IS and
beta-cell function that are independent of weight reduction and specific to RYGB or SG wit...

## Key facts

- **NIH application ID:** 10188510
- **Project number:** 5R01DK072011-15
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** Judith Korner
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $375,242
- **Award type:** 5
- **Project period:** 2005-09-01 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10188510

## Citation

> US National Institutes of Health, RePORTER application 10188510, Metabolic and Endocrine Effects of Bariatric Surgery (5R01DK072011-15). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10188510. Licensed CC0.

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