Chronic Intermittent Low-Pressure Hypoxia Suppresses Inflammation and Regulates Glycolipids by Modulating...

Background/Objectives: Type 2 Diabetes Mellitus (T2DM) is a chronic disease with persistent hyperglycemia as the main clinical manifestation. Chronic Intermittent Hypobaric Hypoxia (CIHH) is a clinical intervention with intermittent low-pressure hypoxic environmental stimulation. The aim of this study was to evaluate the therapeutic effect and anti-inflammatory effect of CIHH in db/db mice. Methods: A simulated 5000 m altitude environment was used to intervene db/db mice. db/db mice were divided into an intervention group (6 h/d) (n = 10) and a control group (n = 10); meanwhile, healthy mice were divided into two groups, the intervention group (6 h/d) (n = 10) and the control group (n = 10). The intervention lasted for 6 weeks. Biochemical analyses and pathological tests were performed to evaluate the therapeutic effects, and for the evaluation of mitochondrial respiration, changes in the respiratory capacity of liver mitochondria at various stages of respiration were examined using Oxygraph-2 k. Changes in inflammatory factors in the liver of mice were analyzed using ELISA. Results: Following CIHH intervention, db/db mice exhibited significant reductions in body weight, food intake, FBG, TC, TG, and LDL, along with increased HDL levels. Liver indices, PEPCK, G-6-phosphate dehydrogenase, and GLUT2 decreased, while GLUT4 and p-AMPK increased. Hepatic HE staining revealed reduced lipid droplets in the liver. HOMA-IR decreased while HOMA-IS increased. Hepatocyte mitochondrial respiration-related indicators CI + CII stage RCR, CII stage RCR, and CI stage SCR increased, while CI stage SCR decreased. Inflammation-related factors NLRP3, TNF-α, IL-1β, and IL-6 decreased in liver tissue. Conclusions: CIHH effectively improves gluconeogenesis and insulin resistance in db/db mice, a result potentially linked to enhanced mitochondrial respiratory capacity and anti-inflammatory effects. Therefore, CIHH offers a potential therapeutic approach for type 2 diabetes.