Abstract
Obesity is associated with a low-grade chronic inflammation state. As a consequence, adipose tissue expresses pro-inflammatory cytokines that propagate inflammatory responses systemically elsewhere, promoting whole-body insulin resistance and consequential islet β-cell exhaustation. Thus, insulin resistance is considered the early stage of type 2 diabetes. However, there is evidence of obese individuals that never develop diabetes indicating that the mechanisms governing the association between the increase of inflammatory factors and type 2 diabetes are much more complex and deserve further investigation. We studied for the first time the differences in insulin signalling and inflammatory pathways in blood and visceral adipose tissue (VAT) of 20 lean healthy donors and 40 equal morbidly obese (MO) patients classified in high insulin resistance (high IR) degree and diabetes state. We studied the changes in proinflammatory markers and lipid content from serum; macrophage infiltration, mRNA expression of inflammatory cytokines and transcription factors, activation of kinases involved in inflammation and expression of insulin signalling molecules in VAT. VAT comparison of these experimental groups revealed that type 2 diabetic-MO subjects exhibit the same pro-inflammatory profile than the high IR-MO patients, characterized by elevated levels of IL-1β, IL-6, TNFα, JNK1/2, ERK1/2, STAT3 and NFκB. Our work rules out the assumption that the inflammation should be increased in obese people with type 2 diabetes compared to high IR obese. These findings indicate that some mechanisms, other than systemic and VAT inflammation must be involved in the development of type 2 diabetes in obesity.
Highlights
Over the last few years, the number of people with diabetes mellitus has massively increased, becoming one of the most important public health challenges globally
A decrease of serum insulin levels and an increase of serum glucose levels were observed in T2D-morbidly obese (MO) patients compared to high insulin resistance (high insulin receptor (IR))-MO subjects
We deepened in the study of the mechanisms involved in the onset of type 2 diabetes mellitus in obesity by analyzing for the first time, serum lipid content, inflammation markers, macrophage infiltration and intracellular pathways in visceral adipose tissue (VAT) from a cohort of extremely well weight/metabolic state matched obese distributed into two experimental groups, high insulin resistant degree and diabetes state
Summary
Over the last few years, the number of people with diabetes mellitus has massively increased, becoming one of the most important public health challenges globally. On the onset of type 2 diabetes mellitus, obesity is the major cause. Only one-third of insulin resistant obese individuals develop type 2 diabetes mellitus. The precise mechanisms that lead to the b-cell dysfunction are incompletely understood, some processes have been postulated such as oxidative stress, endoplasmic reticulum stress, lipotoxicity and increased levels of inflammation [2,3,4]. All these factors may elicit an inflammatory response, whereas some may be the result of the inflammation [5,6]
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