# Impact of dietary lipids on pancreas cancer initiation and progression

> **NIH NIH UH2** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2024 · $257,709

## Abstract

PROJECT SUMMARY
Despite advances in cancer treatment, the five-year survival rate for pancreatic ductal adenocarcinoma (PDA)
is 12%. Obesity has been linked to PDA risk epidemiologically, implying that diet and metabolism have roles in
PDA tumor initiation, but the biological basis for this correlation is not clear. Data from our labs shows that high
fat diet (HFD) can accelerate PDA development in a Ptf1a-Cre/LSL-KrasG12D (KC) mouse model of PDA. Further,
recent work has shown that acute inflammation can epigenetically prime acinar cells in the pancreas for
tumorigenesis. We hypothesize that HFD, which has been clearly demonstrated to alter inflammation in a range
of tissues, can similarly prime the pancreas to promote or prevent tumor development. The two aims in our
proposal investigate effects of two HFDs chosen specifically because they are enriched for classes of fatty acids
known to have distinct biological effects. Aim 1 examines the effects of a HFD comprised of lard (HFLD), which
contains mostly saturated long chain fatty acids that are associated with obesity, on PDA tumorigenesis. To
study how HFLD may prime the pancreas for tumor growth, we will use scRNA-seq and scATAC-seq to define
dietary effects on healthy pancreas. We will also leverage our newly developed CYTO-Tag mouse to rapidly
isolate acinar cells for metabolomics, thus allowing us to draw connections between changes in gene expression,
chromatin structure, and metabolism in acinar cells in the context of HFLD. We will then use a tamoxifen-
inducible Ptf1a-CreERT/LSL-KrasG12D (iKC) model to study the effects of HFLD on tumor growth, and use an
orthotopic tumor model generated from HFLD-conditioned iKC acinar cells to distinguish between acinar cell-
intrinsic and -extrinsic tumor growth mechanisms. In Aim 2, we will examine the effects of a HFD comprised of
coconut oil (HFCD), isocalorically matched with the HFLD, on PDA tumor growth. Coconut oil is comprised of
medium chain saturated fatty acids. It is a common dietary fat “swap” patients use when attempting to eat
healthier, particularly in a ketogenic diet, but the effects of HFCD on PDA tumor growth are not known. We will
use scRNA-seq, scATAC-seq, and our CYTO-Tag mouse to characterize the effects of HFCD on healthy
pancreas, followed by tumor growth experiments in iKC mice. We will begin to pinpoint mechanisms underlying
any observed effects on tumor growth through studies in orthotopic tumor models using HFCD-conditioned
acinar cells. Aim 2 will define the effects of HFCD on tumor growth for the first time, and because our HFLD and
HFCD are isocaloric, we will be able to directly compare effects of these diets on tumor growth. Understanding
the molecular basis underlying differential effects of compositionally distinct HFD will enable more informed
dietary recommendations for patients to potentially reduce cancer risk.

## Key facts

- **NIH application ID:** 10973509
- **Project number:** 1UH2CA286583-01A1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** Heather Christofk
- **Activity code:** UH2 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $257,709
- **Award type:** 1
- **Project period:** 2024-09-05 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10973509

## Citation

> US National Institutes of Health, RePORTER application 10973509, Impact of dietary lipids on pancreas cancer initiation and progression (1UH2CA286583-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10973509. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*