Muscle and adipose tissue morphology, insulin sensitivity and beta-cell function in diabetic and nondiabetic obese patients: effects of bariatric surgery

Abstract

Obesity is characterized by insulin-resistance (IR), enhanced lipolysis, and ectopic, inflamed fat. We related the histology of subcutaneous (SAT), visceral fat (VAT), and skeletal muscle to the metabolic abnormalities, and tested their mutual changes after bariatric surgery in type 2 diabetic (T2D) and weight-matched non-diabetic (ND) patients. We measured IR (insulin clamp), lipolysis (2H5-glycerol infusion), ß-cell glucose-sensitivity (ß-GS, mathematical modeling), and VAT, SAT, and rectus abdominis histology (light and electron microscopy). Presurgery, SAT and VAT showed signs of fibrosis/necrosis, small mitochondria, free interstitial lipids, thickened capillary basement membrane. Compared to ND, T2D had impaired ß-GS, intracapillary neutrophils and higher intramyocellular fat, adipocyte area in VAT, crown-like structures (CLS) in VAT and SAT with rare structures (cyst-like) ~10-fold larger than CLS. Fat expansion was associated with enhanced lipolysis and IR. VAT histology and intramyocellular fat were related to impaired ß-GS. Postsurgery, IR and lipolysis improved in all, ß-GS improved in T2D. Muscle fat infiltration was reduced, adipocytes were smaller and richer in mitochondria, and CLS density in SAT was reduced. In conclusion, IR improves proportionally to weight loss but remains subnormal, whilst SAT and muscle changes disappear. In T2D postsurgery, some VAT pathology persists and beta-cell dysfunction improves but is not normalized.

Nanoparticles

“…Additionally, successful demonstration of targeting to white and brown adipose tissues opens the door to encapsulating different therapeutics in these particles for targeting fatty tissue in diseases where adipose tissue is defective. One possible disease state is diabetes, where adipose tissues shows chronic inflammation 275 . A classical marker of the chronic inflammation in diabetic fatty tissue is crown like structures produced by macrophages 276 .…”

Impact of Duodeno-Jejunal Bypass Liner (EndoBarrierTM) Implantation on Insulin Sensitivity in Patients with Type 2 Diabetes Mellitus (T2DM): A Study Protocol for a Pilot Trial

“…Insulin sensitivity and declining beta-cell function are the key pathophysiologic drivers in T2DM. Previous reports have demonstrated improvements in both parameters in subjects undergoing BS [29], but as yet the effects of a gastro-duodenal bypass liner on these key determinants of glucose metabolism are not well investigated. The results of the first of such studies suggest that positive effects on glucose metabolism occur rapidly after DJBL implantation [27] and that these effects are comparable to those after BS.…”

Metabolic Health, Insulin, and Breast Cancer: Why Oncologists Should Care About Insulin

“…Skeletal muscle biopsy demonstrated increased fat infiltration and adipocyte hypertrophy and a reduction in the number and size of mitochondria. Individuals with type-2 diabetes (relative to obese individual without type-2 diabetes) demonstrated impaired ß-GS, intracapillary neutrophils, and higher intramyocellular fat, adipocyte hypertrophy, and crownlike structures in in both VAT and SAT (95). After bariatric surgery, insulin-resistance and lipolysis both decreased.…”

“…The tissue density of crown-like structures is positively related to adipocyte size, independent of the degree of obesity (93,94). In a sentinel study, Camastra et al (95) investigated the impact of bariatric surgery on (1) measured insulin-resistance (insulin clamp), (2) lipolysis (2H5-glycerol infusion), (3) ßcell glucose-sensitivity (ß-GS, mathematical modeling), and (4) cellular substructure (electron microscopy). Investigators found that pre-surgical subcutaneous fat (SAT) and visceral fat (VAT) demonstrated fibrosis/necrosis, small mitochondria, free interstitial lipids, and a thickened capillary basement membrane (95).…”

“…In a sentinel study, Camastra et al (95) investigated the impact of bariatric surgery on (1) measured insulin-resistance (insulin clamp), (2) lipolysis (2H5-glycerol infusion), (3) ßcell glucose-sensitivity (ß-GS, mathematical modeling), and (4) cellular substructure (electron microscopy). Investigators found that pre-surgical subcutaneous fat (SAT) and visceral fat (VAT) demonstrated fibrosis/necrosis, small mitochondria, free interstitial lipids, and a thickened capillary basement membrane (95). Skeletal muscle biopsy demonstrated increased fat infiltration and adipocyte hypertrophy and a reduction in the number and size of mitochondria.…”