Search Results (4)

Mammary fat plays a profound role in the postnatal development of mammary glands. However, the specific types (white, brown, or beige) of adipocytes in mammary fat and their potential regulatory effects on modulating mammary gland development remain poorly understood. This study aimed to investigate the role of the browning of mammary fat on pubertal mammary gland development and explore the underlying mechanisms. Thus, the mammary gland development and the serum lipid profile were evaluated in mice treated with CL316243, a β3-adrenoceptor agonist, to induce mammary fat browning. In addition, the proliferation of HC11 cells co-cultured with brown adipocytes or treated with the altered serum lipid metabolite was determined. Our results showed that the browning of mammary fat by injection of CL316243 suppressed the pubertal development of mice mammary glands, accompanied by the significant elevation of serum dioleoylphosphocholine (DOPC). In addition, the proliferation of HC11 was repressed when co-cultured with brown adipocytes or treated with DOPC. Furthermore, DOPC suppressed the activation of the PI3K/Akt pathway, while the DOPC-inhibited HC11 proliferation was reversed by SC79, an Akt activator, suggesting the involvement of the PI3K/Akt pathway in the DOPC-inhibited proliferation of HC11. Together, the browning of mammary fat suppressed the development of the pubertal mammary gland, which was associated with the elevated serum DOPC and the inhibition of the PI3K/Akt pathway. Full article

Obesity is the fifth leading cause of death worldwide. In mice and humans with obesity, the adipose organ undergoes remarkable morpho-functional alterations. The comprehension of the adipose organ function and organization is of paramount importance to understand its pathology and formulate future therapeutic strategies. In the present study, we performed anatomical dissections, magnetic resonance imaging, computed axial tomography and histological and immunohistochemical assessments of humans and mouse adipose tissues. We demonstrate that most of the two types of adipose tissues (white, WAT and brown, BAT) form a large unitary structure fulfilling all the requirements necessary to be considered as a true organ in both species. A detailed analysis of the gross anatomy of mouse adipose organs in different pathophysiological conditions (normal, cold, pregnancy, obesity) shows that the organ consists of a unitary structure composed of different tissues: WAT, BAT, and glands (pregnancy). Data from autoptic dissection of 8 cadavers, 2 females and 6 males (Age: 37.5 ± 9.7, BMI: 23 ± 2.7 kg/m²) and from detailed digital dissection of 4 digitalized cadavers, 2 females and 2 males (Age: 39 ± 14.2 years, BMI: 22.8 ± 4.3 kg/m²) confirmed the mixed (WAT and BAT) composition and the unitary structure of the adipose organ also in humans. Considering the remarkable endocrine roles of WAT and BAT, the definition of the endocrine adipose organ would be even more appropriate in mice and humans. Full article

Brown adipose tissue (BAT), which is a thermogenic fat tissue originally discovered in small hibernating mammals, is believed to exert anti-obesity effects in humans. Although evidence has been accumulating to show the importance of BAT in metabolism regulation, there are a number of unanswered questions. In this review, we show the remaining mysteries about BATs. The distribution of BAT can be visualized by nuclear medicine examinations; however, the precise localization of human BAT is not yet completely understood. For example, studies of ¹⁸F-fluorodeoxyglucose PET/CT scans have shown that interscapular BAT (iBAT), the largest BAT in mice, exists only in the neonatal period or in early infancy in humans. However, an old anatomical study illustrated the presence of iBAT in adult humans, suggesting that there is a discrepancy between anatomical findings and imaging data. It is also known that BAT secretes various metabolism-improving factors, which are collectively called as BATokines. With small exceptions, however, their main producers are not BAT per se, raising the possibility that there are still more BATokines to be discovered. Although BAT is conceived as a favorable tissue from the standpoint of obesity prevention, it is also involved in the development of unhealthy conditions such as cancer cachexia. In addition, a correlation between browning of mammary gland and progression of breast cancers was shown in a xenotransplantation model. Therefore, the optimal condition should be carefully determined when BAT is considered as a measure the prevention of obesity and improvement of metabolism. Solving BAT mysteries will open a new door for health promotion via advanced understanding of metabolism regulation system. Full article

MicroRNAs (miRNA) regulate mRNA networks to coordinate cellular functions. In this study, we constructed gene co-expression networks to detect miRNA modules (clusters of miRNAs with similar expression patterns) and miRNA–mRNA pairs associated with blood (triacylglyceride and nonesterified fatty acids) and milk (milk yield, fat, protein, and lactose) components and milk fatty acid traits following dietary supplementation of cows’ diets with 5% linseed oil (LSO) (n = 6 cows) or 5% safflower oil (SFO) (n = 6 cows) for 28 days. Using miRNA transcriptome data from mammary tissues of cows for co-expression network analysis, we identified three consensus modules: blue, brown, and turquoise, composed of 70, 34, and 86 miRNA members, respectively. The hub miRNAs (miRNAs with the most connections with other miRNAs) were miR-30d, miR-484 and miR-16b for blue, brown, and turquoise modules, respectively. Cell cycle arrest, and p53 signaling and transforming growth factor–beta (TGF-β) signaling pathways were the common gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways enriched for target genes of the three modules. Protein percent (p = 0.03) correlated with the turquoise module in LSO treatment while protein yield (p = 0.003) and milk yield (p = 7 × 10⁻⁰⁴) correlated with the turquoise model, protein and milk yields and lactose percent (p < 0.05) correlated with the blue module and fat percent (p = 0.04) correlated with the brown module in SFO treatment. Several fatty acids correlated (p < 0.05) with the blue (CLA:9,11) and brown (C4:0, C12:0, C22:0, C18:1n9c and CLA:10,12) modules in LSO treatment and with the turquoise (C14:0, C18:3n3 and CLA:9,11), blue (C14:0 and C23:0) and brown (C6:0, C16:0, C22:0, C22:6n3 and CLA:10,12) modules in SFO treatment. Correlation of miRNA and mRNA data from the same animals identified the following miRNA–mRNA pairs: miR-183/RHBDD2 (p = 0.003), miR-484/EIF1AD (p = 0.011) and miR-130a/SBSPON (p = 0.004) with lowest p-values for the blue, brown, and turquoise modules, respectively. Milk yield, protein yield, and protein percentage correlated (p < 0.05) with 28, 31 and 5 miRNA–mRNA pairs, respectively. Our results suggest that, the blue, brown, and turquoise modules miRNAs, hub miRNAs, miRNA–mRNA networks, cell cycle arrest GO term, p53 signaling and TGF-β signaling pathways have considerable influence on milk and blood phenotypes following dietary supplementation of dairy cows’ diets with 5% LSO or 5% SFO. Full article