Preprint Review Version 1 Preserved in Portico This version is not peer-reviewed

Molecular Mechanisms of the Vicious Cycle between Insulin Resistance and the Inflammatory Response in Obesity

Version 1 : Received: 13 May 2023 / Approved: 15 May 2023 / Online: 15 May 2023 (10:37:48 CEST)

A peer-reviewed article of this Preprint also exists.

Szukiewicz, D. Molecular Mechanisms for the Vicious Cycle between Insulin Resistance and the Inflammatory Response in Obesity. Int. J. Mol. Sci. 2023, 24, 9818. Szukiewicz, D. Molecular Mechanisms for the Vicious Cycle between Insulin Resistance and the Inflammatory Response in Obesity. Int. J. Mol. Sci. 2023, 24, 9818.

Abstract

The comprehensive anabolic effects of insulin throughout the body, in addition to the control of glycemia, also include ensuring lipid homeostasis and anti-inflammatory modulation, especially in adipose tissue (AT). The prevalence of obesity, defined as a body mass index (BMI) ≥ 30 kg/m2, has been increasing worldwide on a pandemic scale with accompanying syndemic health problems, including glucose intolerance, insulin resistance (IR) and diabetes. Impaired tissue sensitivity to insulin or IR paradoxically leads to diseases with an inflammatory component despite hyperinsulinemia. Therefore, an excess of visceral AT in obesity initiates chronic low-grade inflammatory conditions that interfere with insulin signaling via insulin receptor (INSR). Moreover, in response to IR, hyperglycemia itself stimulates a primarily defensive inflammatory response associated with the subsequent release of numerous inflammatory cytokines and a real threat of organ function deterioration. In this review, all components of this vicious cycle are characterized with particular emphasis on the interplay between insulin signaling and both the innate and adaptive immune responses related to obesity. Increased visceral AT accumulation in obesity should be considered the main environmental factor responsible for the disruption in the epigenetic regulatory mechanisms in the immune system, resulting in autoimmunity and inflammation.

Keywords

insulin resistance; insulin sensitivity; innate immune system, adaptive immune system, inflammatory response; obesity; visceral adipose tissue; insulin; insulin receptor; insulin signaling

Subject

Medicine and Pharmacology, Endocrinology and Metabolism

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