# Microbiota and Inflammation in Adiposity: The Ground Squirrel Model

> **NIH NIH R15** · UNIVERSITY OF WISCONSIN OSHKOSH · 2022 · $426,608

## Abstract

During development of obesity, an altered diet leads to changes in the gut microbiota, including decreased
diversity and shifts in relative abundance of certain phyla. This leads to a pro-inflammatory gut environment,
inflammation in distant tissues (i.e., adipose), accumulation of fat and eventually insulin resistance (IR).
Current rodent models of fat accumulation focus on one etiological cause and use in-bred laboratory strains;
however, translation of these studies to human medicine has been limited, presumably because a) humans are
a heterogeneous outbred population with a more variable microbiota than laboratory rodents, and b) the
development of obesity and IR results from a combination of dietary, metabolic and genetic factors.
Hibernating mammals like 13-lined ground squirrels (Ictidomys tridecemlineatus) naturally increase adiposity
each year during a “pre-hibernation fattening phase”. We have previously shown that this increased adiposity
is accompanied by inflammation of metabolic tissues. Results of our current award show that cecal microbiota
transfer from lean squirrels or supplementation with Akkermansia muciniphila ameliorated some inflammation
in fattening ground squirrels. Treatment with the gut-specific anti-inflammatory drug mesalazine significantly
suppressed inflammation in gut and adipose tissues and increased caloric intake without affecting body mass.
The experiments outlined in this proposal take the next step by using gut microbiota transfer (GMT) to reaffirm
the obesogenic role of the microbiota in ground squirrels by using GMT to transfer the phenotype to mice. We
will then test prebiotic (to increase microbiota diversity) and mesalazine treatments in mice and ground
squirrels to assess whether manipulating the microbiota and immune system together can curb adiposity and
the development of IR. The hypotheses for this investigation are that 1) changes in the gut microbiome and
immune system of squirrels soon after emergence from hibernation encourage adiposity in non-
hibernators and 2) boosting gut microbial diversity with a diet containing prebiotics in conjunction with
mesalazine treatment will ameliorate fat accumulation, metabolic inflammation and IR more effectively
than either treatment alone. The proposed experimental approach uses GMT from fattening ground squirrels
into outbred mouse strains to elucidate the obesogenic properties of the squirrel microbiota. By using GMT of
samples collected at different points post-hibernation, Specific Aim 1 will identify the point at which the ground
squirrel’s microbiota harvest the most energy from the diet. In Specific Aim 2 we will treat fattening ground
squirrels and outbred mice after GMT with prebiotics, mesalazine or both together to evaluate the cumulative
effect of promoting microbiota diversity and curbing inflammation on adiposity. Our experiments promise to
further clarify the role of the gut microbiota and immune system in the accumulation of fat and
developm...

## Key facts

- **NIH application ID:** 10577974
- **Project number:** 2R15GM124586-02
- **Recipient organization:** UNIVERSITY OF WISCONSIN OSHKOSH
- **Principal Investigator:** Courtney C Kurtz
- **Activity code:** R15 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $426,608
- **Award type:** 2
- **Project period:** 2018-07-01 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10577974

## Citation

> US National Institutes of Health, RePORTER application 10577974, Microbiota and Inflammation in Adiposity: The Ground Squirrel Model (2R15GM124586-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10577974. Licensed CC0.

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