(784) The Impact of Pregnancy and Obesity on Glucose Metabolism in Mouse Skeletal Muscle

Friday, January 31, 2025

10:30 AM – 12:30 PM

Submitting Author and Presenting Author(s)

Jenny B. Koenig, MD, PhD

Resident Physician
UC San Diego
La Jolla, CA, United States

Coauthor(s)

ER

Ella Rust

UC San Diego
La Jolla, California, United States
LF

Liam S. Fitzgerald, BS

UC San Diego
La Jolla, California, United States
SS

Simon Schenk, PhD

UC San Diego
La Jolla, California, United States
LB

Lindsey A. Burnett, MD, PhD

Assistant Professor
UC San Diego Medical Center
La Jolla, California, United States

Objective: Obesity affects over 40% of reproductive-aged women in the United States. This study aimed to examine the interactive effects of diet-induced obesity and pregnancy on oral glucose tolerance and skeletal muscle insulin-stimulated glucose uptake in a mouse model of diet-induced obesity.

Study Design: C57/BL6/NJ mice (4 weeks old) were fed a low-fat diet (LFD; 10% of calories from fat) or high-fat diet (HFD; 60% of calories from fat) for 6 weeks before mating. An oral glucose tolerance test (OGTT; 2 g/kg) was conducted in late pregnancy (LP, E12.5-17.5) or in age-matched non-pregnant (NP) mice. Skeletal muscle glucose uptake was assessed using a radiolabeled 2-deoxyglucose (2DG) approach in paired soleus muscle, with and without a physiological insulin concentration (60 µU/mL). Statistical analysis was performed using 2-way ANOVA with appropriate post-hoc analysis and significance of P < 0.05.

Results: NP HFD-fed mice weighed significantly more than LFD-fed controls (30.20 vs. 19.97 g, P < 0.0001). Oral glucose tolerance as measured by area under the curve (AUC) was significantly different between LFD-fed and HFD-fed animals (NP: LFD 18,055 vs. HFD 24,089 mg · min/dL, P < 0.01) but was not between NP and LP within each diet (LFD: NP 18,055 vs. LP 16,074 mg · min/dL, P = 0.66; HFD: NP 24,089 vs. LP 21,311 mg · min/dL, P = 0.32). Specific to skeletal muscle, insulin-stimulated glucose uptake (insulin 2DG uptake minus basal 2DG uptake) was decreased by HFD-feeding (NP: LFD 0.69 vs. HFD 0.29 µmol/20 min/g, P = 0.09; LP: LFD 0.98 vs. HFD 0.19 µmol/20 min/g, P < 0.001), but not by pregnancy (LFD: NP vs. LP, P = 0.28; HFD: NP vs. LP, P = 0.90).

Conclusion: Diet-induced obesity, but not pregnancy, significantly impairs oral glucose tolerance and insulin-stimulated glucose uptake in skeletal muscle. This study provides valuable insights into the interactive effects of pregnancy and obesity on glycemia and skeletal muscle insulin resistance.