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Session: Exemplary Trainee Abstracts in Obesity Science Research (Poster Theater Flash Session 8)

(PTFS08-02-24) The Role of Intestinal Heat-Shock Protein 70 in Altering Dietary Fat Absorption

Sunday, June 30, 2024
2:04 PM – 2:08 PM CT
Location:  W185A-C
Objectives: Heat-shock protein 70 (HSP70) is emerging as a therapeutic target for diet-induced obesity (DIO). Our preliminary data shows that intestinal overexpression of HSP70 (HSP70 transgenic, HSP70TG) are protected from DIO, however further studies are required to elucidate the underlying mechanisms. We hypothesized that HSP70TG mice would display decreased dietary fat absorption vs their non-transgenic (HSP70NTG) littermates.

Methods: To test this hypothesis, HSP70TG and HSP70NTG mice were fed high-fat diet (HFD; 60% kCal from fat) or low-fat diet (LFD; 10% kCal from fat) for 12 weeks (n=3-7). After 10 weeks on diet, mice were fasted 4 hours and given 200 µL olive oil via oral gavage. Blood was collected at 0, 1, 2, 3, and 4 hours. Plasma triacylglycerol (TAG) levels were measured. Next, a 24-hour stool collection was performed for bomb calorimetry. At 12 weeks, mice were fasted 4 hours and treated retro-orbitally with 100 µl 10% tyloxapol for 10 minutes, then orally gavaged with 200 µL olive oil with 2 µCi each of 3H-triolein and 14C-cholesterol. Blood was collected at 1, 3, 5, and 7 hours post gavage and mice were euthanatized. Intestinal mucosal scrapings in 5 equal segments along the small intestine were harvested (S1-S5 proximal to distal relative to stomach), dissolved in SOVABLE and scintillation counting was performed.

Results: HFD fed-HSP70TG mice had significantly increased 24-hour stool kCal vs HSP70NTG littermates (p < 0.01), with no differences in daily kCal absorption. HSP70TG HFD fed mice also displayed significantly reduced digestive efficiency compared to HSP70NTG HFD fed mice (p < 0.01). HSP70TG mice fed HFD also showed altered plasma TAG clearance, handling dietary lipid in a similar manner to LFD fed mice. No clear trends were evident based on plasma 3H and 14C levels, however LFD fed mice displayed a significant decrease in both 3H-triolein and 14C-cholesterol levels in sections S1 and S3 in HSP70TG vs HSP70NTG mice (p < 0.05). Additionally, there was a significant decrease in both 3H-triolein and 14C-cholesterol levels in section S4 in HFD fed-HSP70TG vs HSP70NTG mice (3H p< 0.05; 14C p< 0.01).

Conclusions: In summary, HSP70 overexpression increased caloric excretion in stool of HFD fed-HSP70TG mice, altered dietary lipid handling upon lipid challenge, and decreased levels of fat and cholesterol in the intestinal epithelium.

Funding Sources: NIH NIDDK, DK129890