Dataset Information

A reduced M1-like/M2-like ratio of macrophages in healthy adipose tissue expansion during SGLT2 inhibition.

ABSTRACT: The adipose tissue includes various stromal cells, such as preadipocytes, endothelial cells, fibroblasts, and immune cells, which are involved in adipose tissue functions. We previously reported that, in obese mice, the sodium-glucose cotransporter 2 inhibitor ipragliflozin (Ipra) promoted the expansion of the epididymal adipose tissue (Epi) with increase of serum ketone body concentration. The Ipra-induced adipose tissue expansion did not deteriorate adipose inflammation, or systemic glucose/lipid metabolism, referred to as "healthy adipose tissue expansion." Here we found that Ipra promoted healthy adipose tissue expansion with a reduced ratio of pro-inflammatory M1-like adipose tissue macrophages (ATMs) to anti-inflammatory M2-like ATMs. Ipra downregulated the gene expression of interleukin (IL)-15 (Il15) in stromal cells of Epi. IL-15 inhibited lipogenesis in 3T3-L1 cells associated with downregulation of the lipogenic gene. Ketone body ?-hydroxybutyrate suppressed Il15 gene induction in M1-polarized cultured macrophages, and a ketogenic diet reproduced the adipose tissue expansion without deteriorating systemic glucose metabolism in mice. Our data indicate that the phenotypic switch of ATMs could mediate healthy adipose tissue expansion by treatment with Ipra, and it may offer new insights into the pathophysiological mechanisms of adipose tissue expansion.

SUBMITTER: Miyachi Y

PROVIDER: S-EPMC6208395 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

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A reduced M1-like/M2-like ratio of macrophages in healthy adipose tissue expansion during SGLT2 inhibition.

Miyachi Yasutaka Y Tsuchiya Kyoichiro K Shiba Kumiko K Mori Kentaro K Komiya Chikara C Ogasawara Naomi N Ogawa Yoshihiro Y

Scientific reports 20181031 1

The adipose tissue includes various stromal cells, such as preadipocytes, endothelial cells, fibroblasts, and immune cells, which are involved in adipose tissue functions. We previously reported that, in obese mice, the sodium-glucose cotransporter 2 inhibitor ipragliflozin (Ipra) promoted the expansion of the epididymal adipose tissue (Epi) with increase of serum ketone body concentration. The Ipra-induced adipose tissue expansion did not deteriorate adipose inflammation, or systemic glucose/li ...[more]

PMID: 30382157

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Project description:BackgroundTumor-associated macrophages (TAMs) are classified into two major phenotypes, M1 and M2. M1 TAMs suppress cancer progression, while M2 TAMs promote it. However, little is known regarding the role of TAMs in the development of ovarian cancer. Here, we investigated the relationship between TAM distribution patterns (density, microlocalization, and differentiation) and ovarian cancer histotypes, and we explored whether altered TAM distribution patterns influence long-term outcomes in ovarian cancer patients.MethodsA total of 112 ovarian cancer patients were enrolled in this study, and the subjects were divided into two groups according to their survival (< 5 years vs. ? 5 years). Immunohistochemistry and immunofluorescence were used to determine the density, microlocalization, and differentiation status of TAMs in ovarian cancer tissues for each histotype. Kaplan-Meier survival and multivariate Cox regression analyses were used to evaluate the prognostic significance of TAM-related parameters in ovarian cancer.ResultsTAMs most frequently infiltrated into the cancer tissue of the serous histotype, followed by mucinous, undifferentiated, endometrioid, and clear cell histotypes (p?=?0.049). The islet/stroma ratio of total TAMs varied among the cancer histotypes, with mucinous and undifferentiated cancers displaying the lowest and highest ratios, respectively (p?=?0.005). The intratumoral TAM density significantly increased with increasing cancer stage and grade (p?=?0.023 and 0.006, respectively). However, the overall M1/M2 TAM ratio decreased as the cancer stage increased (p?=?0.012). In addition, the intra-islet M1/M2 ratio inversely correlated with the residual site size (p?=?0.004). Among the TAM-related parameters, only the increased overall and intra-islet M1/M2 TAM ratios displayed prognostic significance in both the Kaplan-Meier survival and multivariate Cox regression analyses; however, the values of these two parameters did not differ significantly among the cancer histotypes.ConclusionsThe patients with increased overall or intra-islet M1/M2 TAM ratios presented with an improved 5-year prognosis. Nevertheless, the TAM distribution patterns did not influence the overall outcomes of different ovarian cancer histotypes.

Dataset Information

A reduced M1-like/M2-like ratio of macrophages in healthy adipose tissue expansion during SGLT2 inhibition.

Publications

A reduced M1-like/M2-like ratio of macrophages in healthy adipose tissue expansion during SGLT2 inhibition.

Similar Datasets

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