Caracterização do perfil inflamatório do secretoma das células de medula óssea na obesidade e sua influência na expressão de TNF-α no tecido adiposo de camundongos obesos

Abstract

Obesity is characterized by excessive accumulation of body fat, representing a serious public health issue. Inadequate eating habits, sedentary lifestyle, genetic, and socioeconomic factors predispose individuals to the development of metabolic syndrome in adulthood, making the fight against this condition a significant challenge. Chronic inflammation in white adipose tissue (WAT) affects various organs, including bone marrow (BM). BM is a diffuse organ, consisting of bone marrow cells (BMCs), which are responsible for producing the secretome. The bone marrow secretome comprises biomolecules capable of promoting immune regulation and tissue repair and is considered a promising strategy for treating metabolic diseases. However, studies show that obesity can modulate the composition and function of the secretome. The objective of this study was to evaluate the therapeutic efficacy of the secretome in resolving chronic inflammation in WAT and hyperglycemia. We subjected male Swiss mice to a model of overfeeding (OG) from the 3rd day of life. At 90 days, we collected and plated 1x105 BMCs for 2-day culture in P0 and 2x105 BMCs for culture in P1, where we evaluated the cytokine profile in the secretome. In the in vivo assays, animals with 90 days, we performed therapeutic application of 400 µL of secretome or 2x105 BMCs intraperitoneally, forming groups subjected to therapy with BMCs or secretome (SB) from healthy animals (OG+SBc or OG+CMOc) and BMCs or SB from overfed animals (OG+SBo or OG+CMOo). After 10 days ther-apy, the animals were sacrificed for measurement of body mass gain, final weight, biometric parameters, glycemia, and immunohistochemistry for TNF-α in WAT. In the P0 secretome results, the cytokines TNF-α, IFN-γ, IL-2, IL-6, IL-17, and IL-4 remained significantly elevated with a significant reduction in IL-10 in OG. In P1, the secretome in OG remained with a significative presence of TNF-α only. In the in vivo assays, the overfeeding model was effective in inducing an obesogenic condition, marked by significant body mass gain, final weight, hyperglycemia, and Lee index in OG. Therapy containing secretome in OG+SBc promoted significant improvement in Lee index, glycemia, and reduced TNF-α expression in WAT mice. Neither supernatant nor bone marrow cells from overfed animals were effective in alleviating hyperglycemia and inflammation in WAT. This investigation may pave the way for a better understanding of the impacts of obesity on the cellular and paracrine mechanisms of the secretome, allowing selection for clinical purposes and reinforcing research toward secretome-based therapy applied to nanotechnology in individuals with metabolic diseases.