Profile of insulin resistance in adipose tissue of diet induced obese mice in response to anti‐obesity treatment

Adipose tissue is an insulin-responsive organ that contributes to both glucose and lipid metabolism. Insulin resistance (IR) is when insulin-dependent tissues lose their sensitivity to insulin, resulting in high blood glucose and insulin due to impairment of the negative feedback mechanism. Insulin resistance progress to metabolic disorders like obesity and type 2 diabetes. Sulforaphane (SFN) is a potential anti-obesity drug under investigation.This study aims to understand the effect of SFN on insulin resistance pathways in adipose tissues of diet induced obese (DIO) mice.Wild-type CD1 male mice were fed a high-fat diet (HFD) for 16 weeks to induce obesity. Mice were divided into two groups DIO-SFN and DIO-V. DIO mice have been injected via IP route by SFN (5 mg/kg BW) or Vehicle (25μl) for 4 weeks. Daily body weight measurements have been recorded, and glucose tolerance test (GTT) at day 21 after injection and insulin tolerance test (ITT) at day 25 after injection. Subsequently, mice were sacrificed, blood and tissue samples were collected and snap-frozen instantly. Total RNA was extracted from epididymal white adipose tissue (eWAT). Plasma leptin, insulin, and glucose level were measured, and 84 IR genes in adipose tissues were examined using RT-PCR array technology.SFN treatment to DIO mice causes a significant reduction in body weight by 18.4%. Furthermore, SFN causes a significant reduction in circulating leptin concentrations in DIO-SFN compared to the vehicle-treated group. SFN is associated with the improvement of GTT and ITT. SFN causes dysregulation of eight genes related to inflammation, adipocytokine signaling, Il-6, and HMGB1 pathways. SFN treatment causes significant changes in functions related to adipose tissue insulin resistance such as inhibition of chemotaxsis, inflammatory response and lipid accumulation.This study demonstrated that SFN treatment effectively reduces body weight and can ameliorate IR in eWAT via inhibition of pathways mainly related to inflammation, such as adipocytokine signaling, Il-6, and HMGB1. SFN can be considered a future anti-obesity drug.