Increased mast cell abundance in adipose tissue of metabolic syndrome: relevance to the proinflammatory state and increased adipose tissue fibrosis.

Metabolic Syndrome (MetS) affects 35% of American adults > 40 yr and portends an increased risk for both atherosclerotic cardiovascular disease (ASCVD) and diabetes. The role of mast cells in the proinflammatory state of MetS is not well elucidated. We propose that mast cells in subcutaneous adipose tissue (SAT) of MetS patients without diabetes or clinical ASCVD contribute to insulin resistance and inflammation. Matched controls ( n = 15) and MetS ( n = 19) subjects were recruited from Sacramento, CA, and selected based on Adult Treatment Panel III criteria. SAT biopsy was performed on all subjects and processed for immunohistochemistry. The SAT sections were stained using Astra Blue stain and tryptase stain for mast cells. Fasting blood was obtained for chemistries and biomarkers. Abundance of mast cells (Astra Blue stain) in SAT of MetS subjects compared with controls was increased 2.5-fold ( P < 0.0001). Mast cells correlated positively and significantly with waist circumference, glucose, triglycerides, homeostatic model of assessment-insulin resistance (HOMA-IR), AT insulin resistance, leptin, interleukin (IL)-1ß, IL-6, chemerin, p38 MAPK activity, and nuclear factor κB activity in circulating monocytes. Mast cells also correlated significantly with markers of fibrosis and angiogenesis. Tryptase staining of mast cells in AT revealed a significant increase ( P = 0.008) with similar correlations. We make the novel observation that there are increased mast cells in SAT of MetS, and these mast cells correlate with insulin resistance (hepatic and adipose tissue), inflammation, and AT fibrosis. Hence, these immune cells appear to occupy a pivotal role in the pathogenesis of MetS.

Hepatitis C Virus Elimination in the United States: Challenges, Progress, and Future Steps.

Hepatitis C virus (HCV) infection is a major public health challenge with a simple, highly efficacious, all-oral therapy (direct-acting antivirals) that can achieve cure. Owing to the ease of treatment, the World Health Organization outlined goals to eliminate HCV by the year 2030. However, unforeseen challenges have hampered progress, and few countries are on track to meet these goals. Significant disparities remain among priority populations because of barriers to care on the systemic, provider, and patient levels. In turn, many local, state, and national organizations have been persistent in tackling these barriers, the greatest of which is linkage to care. In 2023, the White House launched a multipronged national initiative to eliminate HCV infection. The resulting economic impact of the national HCV elimination program is estimated to yield a significant net cost savings of $18.1 billion within a 10-year period. This article addresses the barriers to HCV care in different priority populations and discusses innovative models of HCV care that have been introduced in the United States.

Increased eosinophils in adipose tissue of metabolic syndrome.

AIMS: Metabolic Syndrome (MetS) is a common global disorder that predisposes to both Type 2 diabetes mellitus (T2DM) and cardiovascular disease (ASCVD). Adipose tissue (AT) contributes significantly to increased inflammation and insulin resistance (IR) in MetS which appear to be the crucial underpinnings of MetS. Compared to macrophages and lymphocytes in human subcutaneous AT (SAT), there is sparse data on the role of other immune cells, especially eosinophils (EOS). In this study, we investigated the abundance of EOS in the SAT of 19 patients with MetS without diabetes, ASCVD, smoking or any inflammatory condition, and matched controls. METHODS: SAT EOS were quantified by immunohistochemistry. RESULTS: Both circulating and SAT EOS were significantly increased 2-fold in MetS and correlated with each other. Circulating EOS correlated significantly with triglycerides (TG), high-sensitivity CRP, leptin, and IL-6. SAT EOS correlated significantly with plasma glucose, TG, FFA, adipose-IR, leptin, IL-6, endotoxin, chemerin and inversely with adiponectin. They also correlated with SAT markers of fibrosis: collagen and Sirius red staining of SAT. CONCLUSION: We make the novel and seminal observation that eosinophils are increased in SAT of MetS patients, and are associated with the pro-inflammatory state. Hence, in humans, they appear to contribute to the dysregulation of SAT biology in MetS.