Thirty days of double-strain probiotic supplementation increases monocyte phagocytosis in marathon runners.

Marathon runners, subjected to intense training regimes and prolonged, exhaustive exercises, often experience a compromised immune response. Probiotic supplementation has emerged as a potential remedy to mitigate the impact of prolonged exercise on athletes. Consequently, this study sought to assess the influence of probiotic supplementation on monocyte functionality both before and after the official marathon race. Twenty-seven runners were randomly and double-blindly assigned to two groups: Placebo-PLA (n=13) and Probiotic-PRO (n=14). Over thirty days, both groups received supplements-PLA sachets containing maltodextrin (5g/day) and PRO sachets containing 1 x 1010 CFU Lactobacillus acidophilus and 1 x 1010 CFU Bifidobacterium bifidum subsp. lactis. Blood samples were collected, and immunological assays, including phagocytosis, hydrogen peroxide production, cytokine levels, and monocyte immunophenotyping, were conducted at four different intervals: Baseline (start of supplementation/thirty days pre-marathon), 24h-Before (one-day pre-marathon), 1h-After (1h post-marathon), and 5d-After (five days post-marathon). Monocyte populations remained consistent throughout the study. A notable increase in phagocytosis was observed in the PRO group after thirty days of supplementation. Upon LPS stimulation, both PRO and PLA groups exhibited decreased IL-8 production. However, after the marathon race, IL-15 stimulation demonstrated increased levels of 5d-After, while IL-1-ß, IL-8, IL-10, IL-15, and TNF-α varied across different intervals, specifically within the PRO group. Probiotic supplementation notably enhanced the phagocytic capacity of monocytes. However, these effects were not sustained post-marathon.

Pharmacological Strategies for Insulin Sensitivity in Obesity and Cancer: Thiazolidinediones and Metformin.

BACKGROUND: Chronic diseases, such as obesity and cancer, have high prevalence rates. Both diseases have hyperinsulinemia, hyperglycemia, high levels of IGF-1 and inflammatory cytokines in common. Therefore, these can be considered triggers for cancer development and growth. In addition, low-grade inflammation that modulates the activation of immune cells, cellular metabolism, and production of cytokines and chemokines are common in obesity, cancer, and insulin resistance. Pharmacological strategies are necessary when a change in lifestyle does not improve glycemic homeostasis. In this regard, thiazolidinediones (TZD) possess multiple molecular targets and regulate PPARγ in obesity and cancer related to insulin resistance, while metformin acts through the AMPK pathway. OBJECTIVE: The aim of this study was to review TZD and metformin as pharmacological treatments for insulin resistance associated with obesity and cancer. CONCLUSION: Thiazolidinediones restored adiponectin secretion and leptin sensitivity, reduced lipid droplets in hepatocytes and orexigen peptides in the hypothalamus. In cancer cells, TZD reduced proliferation, production of reactive oxygen species, and inflammation by acting through the mTOR and NFκB pathways. Metformin has similar effects, though these are AMPK-dependent. In addition, both drugs can be efficient against certain side effects caused by chemotherapy.

Metformin Mitigates Fibrosis and Glucose Intolerance Induced by Doxorubicin in Subcutaneous Adipose Tissue.

Doxorubicin (DX) is a chemotherapeutic drug that is used in clinical practice that promotes deleterious side effects in non-tumor tissues such as adipose tissue. We showed that DX leads to extensive damage in adipose tissue via a disruption in 5'-adenosine monophosphate-activated protein kinase (AMPK) and PPAR-gamma signaling. Thus, we investigated whether co-treatment with the biguanide drug metformin (MET) could prevent the side effects of DX through the activation of AMPK in adipose tissue. The goal of the present study was to verify the effects of DX and adjuvant MET treatment in subcutaneous adipose tissue (SAT) and to determine whether MET could protect against chemotherapy-induced side effects. C57/BL6 mice received DX hydrochloride (2.5 mg/kg) intraperitoneally 2 times per week for 2 weeks (DX), concomitantly or not, with MET administration (300 mg/kg oral daily) (DX + MET). The control group (CTRL) was pair-fed according to the food consumption of the DX group. After euthanasia, adipose tissue fat pads were collected, and SAT was extracted so that adipocytes could be isolated. Glucose uptake was then measured, and histological, gene, and protein analyses were performed. One-way analysis of variance was also performed, and significance was set to 5%. DX reduced retroperitoneal fat mass and epididymal pads and decreased glycemia. In cultured primary subcutaneous adipocytes, mice in the DX group had lower glucose uptake when stimulated with insulin compared with mice in the CTRL group. Adipocytes in the DX group exhibited a reduced area, perimeter, and diameter; decreased adiponectin secretion; and decreased fatty acid synthase gene expression. SAT from MET-treated mice also showed a reduction in collagen deposition. Treatment with MET prevented fibrosis and restored glucose uptake in SAT after insulin stimulation, yet the drug was unable to prevent other side effects of DX such as tissue loss and inflammatory response.