Diversity Outbred Mouse Model Recapitulates Human Heterogeneity in the Development of Western Diet-Induced Complications

• DOI: 10.1152/physiol.2024.39.s1.2022
• Publication Date: 2024-05-21T14:57:50Z
• Authors: Kishore Chittimalli; Andrew Tolle; Mansib Rahman; Yagna Jarajapu
• Keywords: 0303 health sciences; 03 medical and health sciences

Background: Diet-induced obesity (DIO) increases risk for cardiovascular disease largely due to compromised gut barrier integrity and systemic inflammation. Animal models understanding the pathophysiology of complications associated with DIO do not take address genetic factors, which determine individual variation in susceptibility develop complications. Hypothesis: DO mice recapitulate heterogeneity western diet-induced metabolic syndrome, disruption Methods: were fed either control (CD) or diet (WD) (Teklad) (n = 10) 16 weeks. Blood glucose levels, tolerance intestinal permeability determined. Inflammatory cells bone marrow blood characterized basal conditions response hindlimb ischemia (HLI). flow recovery following HLI was measured by using Laser Doppler Imaging system intestinal-stem-cells (ISCs) markers, Lgr5, Olfm4 Wnt3. Results: Wide weight gain, hyperglycemia observed WD 10). Similarly, wide Wnt3 expression density ISCs colon on WD. Heterogeneity ISC layer correlated induced compared CD ( p < 0.05, n The number inflammatory (monocytes – CD45 + Ly6G − Ly6C CD115 , neutrophils - pro-inflammatory macrophages CD11b F4/80 CCR2 CD80 anti-inflammatory CX3CR1 CD206 ) BM showed WD-DO accordance variability tolerance. Accordingly, three showing full recovery, mobilization 9). Conclusion: mouse model depicts human diversity WD-induced changes integrity, inflammation ischemic vascular repair therefore serves as a suitable evaluating pharmacological agents that would be effective diverse population. Jackson Laboratory Diversity Outbred Pilot Award National Institute Aging (AG056881). This is abstract presented at American Physiology Summit 2024 meeting only available HTML format. There are no additional versions content this abstract. involved peer review process.