Macrophage-Targeted Therapeutics for Metabolic Disease

Abstract

Macrophages are cells of the innate immune system that are resident in all tissues, including metabolic organs such as the liver and adipose tissue (AT). Because of their phenotypic flexibility, they play beneficial roles in tissue homeostasis, but they also contribute to the progression of metabolic disease. Thus, they are ideal therapeutic targets for diseases such as insulin resistance (IR), nonalcoholic fatty liver disease (NAFLD), and atherosclerosis. Recently, discoveries in the area of drug delivery have facilitated phenotype-specific targeting of macrophages. In this review we discuss advances in potential therapeutics for metabolic diseases via macrophage-specific delivery. We highlight micro- and nanoparticles, liposomes, and oligopeptide complexes, and how they can be used to alter macrophage phenotype for a more metabolically favorable tissue environment.

Hepatocyte sortilin 1 knockout and treatment with a sortilin 1 inhibitor reduced plasma cholesterol in Western diet-fed mice

“…Therefore, in contrast to hepatocyte Sort1 deficiency, myeloid Sort1 deficiency did not seem to provide beneficial effects in maintaining lipid homeostasis and reducing pro-inflammatory response in WD-fed mice. Macrophages play important roles in the pathogenesis of fatty liver disease (40). How macrophage Sort1 deficiency may alter macrophage function to promote hepatocyte lipid accumulation upon WD feeding requires further investigation and is out of the scope of the current study.…”

Unveiling the pathophysiology of gestational diabetes: Studies on local and peripheral immune cells

“…The tissue macrophages at maternal‐foetal interface are named placental Hofbauer cells. The M1 and M2 profile is different during pregnancy progress, and changes in this balance have been associated with obstetric and metabolic disorders …”

“…The M1 and M2 profile is different during pregnancy progress, and changes in this balance have been associated with obstetric and metabolic disorders. 16,20 Dendritic cell (DC) seems to play a critical role in pregnancy development; its interaction with Tregs has been associated with the process of foetal-maternal tolerance. 21,22 Likewise, impaired function and/or number of DC have been demonstrated in obstetric pathologies.…”

Adipose Tissue Macrophage Phenotypes and Characteristics: The Key to Insulin Resistance in Obesity and Metabolic Disorders

“…Macrophages are cells involved in the innate immune system that respond to acute infections and maintain tissue homeostasis by secreting specific chemokines and cytokines . A variety of studies have shown that tissue macrophages can regulate insulin sensitivity in various target tissues such as adipose tissue (e.g., ATM), liver (e.g., Kupffer cells [KCs]), and brain (e.g., microglia).…”