Morphological Preconditions of Metabolic Disorders in the Comorbid Course of Inflammatory Processes in the Lungs and Type 2 Diabetes Mellitus in Rats

Abstract

Objective — to characterize ultrastructural changes in lung and liver cells associated with disturbances in energy metabolism during the comorbid course of inflammation in the lungs and type 2 diabetes mellitus (T2DM). Materials and methods. The study was conducted on adult Wistar rats, divided into four groups: 1) control; 2) rats with simulated inflammation by lipopolysaccharide (LPS) administration (0.5 mg/kg intraperitoneally); 3) rats with insulin resistance induced by a high-fat diet (58 % of total calorie intake from lipids) and LPS injection on the 24th day of the experiment; 4) rats with simulated T2DM by a high-fat diet, streptozotocin injection (25 mg/kg body weight) on the 14th day, and LPS injection on the 24th day of the experiment. The ultrastructure of lung and liver cells was evaluated by electron microscopy in tissue samples obtained from anesthetized animals three days after LPS administration. Results and discussion. In the simulation of inflammation induced by LPS-mediated cytokine mechanisms, inflam­matory symptoms were observed in the lungs, with alveolar type II cells showing mitochondrial dysfunc­tion, a large number of free and attached ribosomes, indicating disruptions in energy metabolism, and the development of compensatory-adaptive reactions (intensification of protein synthesis, reparative processes in mitochondria and their interaction with the endoplasmic reticulum). In the comorbid course of LPS-in­duced inflammation in the lungs and T2DM, enhanced inflammatory manifestations in the lungs were registered against the background of lipid infiltration, increased aero-hydrate barrier hydration, endothelial dysfunction and signs of mitochondrial dysfunction in alveolar type II cells. Compensatory protein synthesis increased, indicating the intensification of alteration processes, and worsening of energy and lipid metabolism. In the simulation of LPS-induced inflammation in the lungs with insulin resistance, pathological manifestations were less pronounced, and mitochondrial dysfunction was not observed, indicating the maintenance of energy metabolism under these conditions, with insulin resistance playing a partial role in the unfavourable course of comorbid pathology. In the liver, during the comorbid course of LPS-induced inflammation in the lungs and T2DM, increased steatosis, endothelial dysfunction, signs of mitochondrial dysfunction in hepatocytes, pronounced compensatory protein synthesis in bound ribosomes, and the formation of endoplasmic reticulum-associated membranes with mitochondria were detected. Conclusions. During the comorbid course of LPS-induced lung inflammation and T2DM, disruptions in energy metabolism intensify, mediated by respiratory and mitochondrial dysfunction, and compensatory protein synthesis and interaction of mitochondria with the endoplasmic reticulum are enhanced. The results suggest that the pathogenesis of comorbid inflammation in the lungs and T2DM or insulin resistance occurs through possible compensation of carbohydrate and energy metabolism disorders at the expense of worsening lipid metabolism and progression of obesity.