Macrophage‐Derived microRNA‐155 Increases in Obesity and Influences Adipocyte Metabolism by Targeting Peroxisome Proliferator‐Activated Receptor Gamma

Abstract

Objective This study aimed to investigate cellular sources of microRNAs (miRNA) within adipose tissue and the impact of obesity on miRNA expression, as well as to examine targets of miRNAs. Methods miRNA expression by quantitative polymerase chain reaction was examined in adipocytes, adipose tissue macrophages (ATM), and peripheral blood mononuclear cells from and individuals with normal weight and with obesity. Differentiated 3T3‐L1 adipocytes were cocultured with macrophages, and 3T3‐L1 and differentiated human mesenchymal stem cells were transfected with miR‐155, with peroxisome proliferator‐activated receptor gamma (PPAR‐γ) and solute carrier family 2 member 4 (GLUT4) abundance measured via Western blot analysis. Results Abundance of miR‐155 and miR‐210 was increased in ATM of participants with obesity by 6.7‐fold and 2.9‐fold (P = 0.002 and P = 0.013, respectively). miR‐130b expression was increased 1.8‐fold in ATM and 4.3‐fold in adipocytes from participants with obesity (P = 0.007 and P = 0.02, respectively). PPARG mRNA expression decreased 32% (P = 0.044) in adipocytes from individuals with obesity. In 3T3‐L1 cells exposed to macrophages, PPARG expression decreased 99.4% (P = 0.02). PPAR‐γ protein content declined 75% (P = 0.001) in 3T3‐L1 cells transfected with miR‐155. GLUT4 protein levels were reduced by 55% (P = 0.021) in differentiated human mesenchymal stem cells exposed to miR‐155. Conclusions Adipose tissue miRNAs are influenced in a cell type–specific fashion by obesity, with macrophage miR‐155 potentially impacting neighboring adipocytes.

Exosomes derived from M0, M1 and M2 macrophages exert distinct influences on the proliferation and differentiation of mesenchymal stem cells

“…In addition, researchers discovered that Mφs in adipose tissue can transport miRNAs through exosomes which finally influence the insulin sensitivity and glucose homeostasis (Ying et al, 2017). Evidence also confirmed that Mφ-derived microRNA can influence adipocyte metabolism (Tryggestad et al, 2019). These all indicate that Mφ-derived exosomes may also participate in the adipogenic differentiation of MSCs.…”

Adipocyte, Immune Cells, and miRNA Crosstalk: A Novel Regulator of Metabolic Dysfunction and Obesity

“…Another miR-155 is overexpressed in obese ATMs and targets peroxisome proliferator-activated receptors (PPARγ). These miRs enter in insulin-secreting pancreatic islets of β cells through endocrine or paracrine regulation via robust effects on cellular insulin action to maintain glucose homeostasis [ 90 ]. miR-34a is identified as a vital mediator and attack on adipose-resident M2 macrophage to stimulate obesity and chronic inflammation [ 91 ].…”

Human Milk Exosomal MicroRNA: Associations with Maternal Overweight/Obesity and Infant Body Composition at 1 Month of Life

“…Among all body fluids, HM is one of the richest sources of miRNAs [ 11 ]. These small, non-coding RNAs bind to complementary sequences within the 3′ untranslated region of messenger RNAs (mRNAs) and thereby modulate protein production, typically by degrading or repressing translation of targeted mRNAs [ 12 , 13 , 14 , 15 ]. They have been shown to function in multiple biological processes, including pathways involved in adipocyte differentiation, insulin signaling, and glucose metabolism [ 16 , 17 ].…”