Intravenous Arginine Administration Attenuates the Inflammatory Response and Improves Metabolic Profiles in Diet-Induced Obese Mice after Sleeve Gastrectomy.

Ya-Ling Chen,Sung-Ling Yeh,Chiu-Li Yeh,Ming-Tsan Lin,Wan-Hsuan Wang

doi:10.3390/metabo12020153

Abstract

Sleeve gastrectomy (SG) is a bariatric surgery that can effectively reduce weight and improve obesity-associated comorbidities. However, surgical stress intensifies inflammation and imbalanced metabolic profiles. Arginine (Arg) is a nutrient with immunomodulatory and anti-inflammatory properties. This study evaluated the short-term effects of Arg administration on adipocyte inflammation and metabolic alterations in obese mice after SG. Mice were assigned to normal and high-fat diet (HFD) groups. After 16 weeks, the HFD group were divided to sham (SH), SG with saline (SS), or Arg (SA) groups. SS and SA groups were postoperatively injected with saline or Arg via the tail vein and sacrificed at day 1 or 3 after the SG, respectively. Results showed that obesity caused elevated plasma glucose and leptin levels. The SG operation enhanced the expression of inflammatory cytokines and macrophage infiltration in adipose tissues, whereas hepatocyte gene expressions associated with lipid β-oxidation were downregulated. Arg treatment reversed the expressions of β-oxidation-associated genes and reduced lipid peroxide production in the liver. Additionally, adipose tissue expressions of inflammatory chemokines were reduced, while the M2 macrophage marker increased after surgery. The findings suggest that postoperative Arg administration elicited more balanced hepatic lipid metabolism, polarized macrophages toward the anti-inflammatory type, and attenuated adipocyte inflammation shortly after SG.

Highlights

Obesity is a worldwide epidemic, and the prevalence has dramatically increased over the past two decades in Taiwan [1]
High-fat diet (HFD) feeding resulted in significant Body Weights (BWs), epididymal fat gain, and higher blood glucose levels at 60, 90, and 120 min after glucose loading
There were no differences in body weight changes and epididymal fat weights between the SG with saline (SS) and SA groups at each time point (Table 1)

Summary

Introduction

Obesity is a worldwide epidemic, and the prevalence has dramatically increased over the past two decades in Taiwan [1]. Excessive adipose tissue accumulation and enlarged adipocytes result in macrophage infiltration and persistent inflammation, which may lead to insulin resistance, dysregulated lipid metabolism, and other metabolic dysfunctions [2]. Weight reduction is an effective strategy in attenuating obesity-related complications. A low-caloric diet, behavior modifications, and drug interventions are commonly used strategies; these conservative treatments have limited effects on long-term weight control, especially in subjects with morbid obesity [3,4]. Sleeve gastrectomy (SG) is a bariatric surgery that is frequently used and considered to be effective for losing weight and associated comorbidities in morbid obesity [5,6]. Obesity delays wound healing [7], and surgical stress itself intensifies inflammatory reactions and imbalanced metabolic profiles [8] that need to be corrected in order to improve subsequent outcomes for the long term

Methods

Results

Conclusion