Diverse Impact of N-Acetylcysteine or Alpha-Lipoic Acid Supplementation during High-Fat Diet Regime on Matrix Metalloproteinase-2 and Matrix Metalloproteinase-9 in Visceral and Subcutaneous Adipose Tissue.

BACKGROUND/AIMS: The high-fat diet (HFD) regime causes obesity and contributes to the development of oxidative stress in the cells by the production of reactive oxygen species and the occurrence and progress of inflammation. Despite years of studies, there is no data explaining the mechanism of action of N-acetylcysteine (NAC) or alpha-lipoic acid (ALA) on matrix metalloproteinase-2 (MMP2) and matrix metalloproteinase-9 (MMP9) in visceral and subcutaneous adipose tissue of HFD-fed rats. Our experiment aimed to evaluate for the first time the influence of chronic antioxidants administration on MMPs biology after an HFD regime as a potential therapeutic strategy for obesity-related complications prevention. METHODS: Male Wistar rats were fed a standard rodent chow or an HFD with intragastric administration of NAC or ALA for ten weeks. The collected samples were subjected to pathohistological evaluation. Real-time PCR and western blot approaches were used to check whether NAC or ALA impacts MMP2/9 expression. RESULTS: Antioxidant supplementation markedly reduced the number of circulating inflammatory cytokines, and tissue macrophage infiltration. Moreover, NAC and ALA have a divergent impact on MMP2 and MMP9 expression in different adipose tissue localization. CONCLUSION: Based on our results, we speculate that NAC and ALA have a prominent effect on the MMP2/9 functions under obesity conditions.

Recent Advances in the Treatment of Insulin Resistance Targeting Molecular and Metabolic Pathways: Fighting a Losing Battle?

Diabetes Mellitus (DM) is amongst the most notable causes of years of life lost worldwide and its prevalence increases perpetually. The disease is characterized as multisystemic dysfunctions attributed to hyperglycemia resulting directly from insulin resistance (IR), inadequate insulin secretion, or enormous glucagon secretion. Insulin is a highly anabolic peptide hormone that regulates blood glucose levels by hastening cellular glucose uptake as well as controlling carbohydrate, protein, and lipid metabolism. In the course of Type 2 Diabetes Mellitus (T2DM), which accounts for nearly 90% of all cases of diabetes, the insulin response is inadequate, and this condition is defined as Insulin Resistance. IR sequela include, but are not limited to, hyperglycemia, cardiovascular system impairment, chronic inflammation, disbalance in oxidative stress status, and metabolic syndrome occurrence. Despite the substantial progress in understanding the molecular and metabolic pathways accounting for injurious effects of IR towards multiple body organs, IR still is recognized as a ferocious enigma. The number of widely available therapeutic approaches is growing, however, the demand for precise, safe, and effective therapy is also increasing. A literature search was carried out using the MEDLINE/PubMed, Google Scholar, SCOPUS and Clinical Trials Registry databases with a combination of keywords and MeSH terms, and papers published from February 2021 to March 2022 were selected as recently published papers. This review paper aims to provide critical, concise, but comprehensive insights into the advances in the treatment of IR that were achieved in the last months.

Diverse impact of N-acetylcysteine or alpha-lipoic acid supplementation during high-fat diet regime on fatty acid transporters in visceral and subcutaneous adipose tissue.

PURPOSE: Adipose tissue's (AT) structural changes accompanying obesity may alter lipid transport protein expression and, thus, the fatty acids (FAs) transport and lipid balance of the body. Metabolic abnormalities within AT contribute to the elevated production of reactive oxygen species and increased oxidative/nitrosative stress. Although compounds such as N-acetylcysteine (NAC) and α-lipoic acid (ALA), which restore redox homeostasis, may improve lipid metabolism in AT, the mechanism of action of these antioxidants on lipid metabolism in AT is still unknown. This study aimed to examine the impact of NAC and ALA on the level and FA composition of the lipid fractions, and the expression of FA transporters in the visceral and subcutaneous AT of high-fat diet-fed rats. MATERIALS AND METHODS: Male Wistar rats were randomly divided into four groups. The mRNA levels and protein expression of FA transporters were assessed using real-time PCR and Western Blot analyses. The collected samples were subjected to histological evaluation. The level of lipids (FFA, DAG, and TAG) was measured using gas-liquid chromatography. RESULTS: We found that antioxidants affect FA transporter expressions at both the transcript and protein levels, and, therefore, they promote changes in AT's lipid pools. One of the most remarkable findings of our research is that different antioxidant molecules may have a varying impact on AT phenotype. CONCLUSION: NAC and ALA exert different influences on AT, which is reflected in histopathological images, FA transport proteins expression patterns, or even the lipid storage capacity of adipocytes.

The Causes of Insulin Resistance in Type 1 Diabetes Mellitus: Is There a Place for Quaternary Prevention?

Diabetes mellitus was the first non-communicable disease that was recognized by the United Nations as a 21st-century pandemic problem. Recent scientific reports suggest that people with type 1 diabetes mellitus also develop insulin resistance, which is generally considered to be a distinctive feature of type 2 diabetes mellitus. The causes of insulin resistance in type 1 diabetes mellitus were explored, but there was a lack of publications that connected the risk factors of insulin resistance in type 1 diabetes mellitus with the proposition of repair mechanisms that are offered by quaternary prevention. Toward this end, the present review is an attempt to combine the previous reports on the causes of insulin resistance in type 1 diabetes mellitus and a brief review of quaternary prevention. The destructive effect of insulin resistance on many physiological processes that predisposes the individual to chronic diabetes complications creates an urgent need to introduce effective therapeutic methods for preventing the development and progression of this pathology.