Fatty diabetic lung: altered alveolar structure and surfactant protein expression.
Pulmonary dysfunction develops in type 2 diabetes mellitus (T2DM) in direct correlation with glycemia and is exacerbated by obesity; however, the associated structural derangement has not been quantified. We studied lungs from obese diabetic (fa/fa) male Zucker diabetic fatty (ZDF) rats at 4, 12, and 36 wk of age, before and after onset of T2DM, compared with lean nondiabetic (+/+) rats. Surfactant proteins A and C (SP-A and SP-C) immunoexpression in lung tissue was quantified at ages 14 and 18 wk, after the onset of T2DM. In fa/fa animals, lung volume was normal despite obesity. Numerous lipid droplets were visible within alveolar interstitium, lipofibroblasts, and macrophages, particularly in subpleural regions. Total triglyceride content was 136% higher. By 12 wk, septum volume was 21% higher, and alveolar duct volume was 36% lower. Capillary basement membrane was 29% thicker. Volume of lamellar bodies was 45% higher. By age 36 wk, volumes of interstitial collagen fibers, cells, and matrix were respectively 32, 25, and 80% higher, and capillary blood volume was 18% lower. ZDF rats exhibited a strain-specific increase in resistance of the air-blood diffusion barrier with age, which was exaggerated in fa/fa lungs compared with +/+ lungs. In fa/fa lungs, SP-A and SP-C expression were elevated at age 14-18 wk; the normal age-related increase in SP-A expression was accelerated, whereas SP-C expression declined with age. Thus lungs from obese T2DM animals develop many qualitatively similar changes as in type 1 diabetes mellitus but with extensive lipid deposition, altered alveolar type 2 cell ultrastructure, and surfactant protein expression patterns that suggest additive effects of hyperglycemia and lipotoxicity.
Foster
David J
DJ
Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390-9034, USA.
Ravikumar
Priya
P
Bellotto
Dennis J
DJ
Unger
Roger H
RH
Hsia
Connie C W
CC
D000375:Aging / Q000473:pathology; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000150:complications* / Q000473:pathology*; D009765:Obesity / Q000150:complications* / Q000473:pathology*; D009929:Organ Size; D011650:Pulmonary Alveoli / Q000378:metabolism* / Q000473:pathology* / Q000648:ultrastructure; D011663:Pulmonary Surfactants / Q000378:metabolism*; D051381:Rats; D011924:Rats, Zucker; D013499:Surface Properties; D013851:Thinness; D014280:Triglycerides / Q000378:metabolism
D011663:Pulmonary Surfactants; D014280:Triglycerides