ABSTRACT
Lactate sits at the crossroad of metabolism, immunity, and inflammation. The expression of cellular lactate transporter MCT1 (known as Slc16a1) increases during immune cell activation to cope with the metabolic reprogramming. We investigated the impact of MCT1 deficiency on CD8+ T cell function during obesity-related inflammatory conditions. The absence of MCT1 impaired CD8+ T cell proliferation with a shift of ATP production to mitochondrial oxidative phosphorylation. In Slc16a1 f/f Tcell cre mice fed a high-fat diet, a reduction in the number of CD8+ T cells, which infiltrated epididymal visceral adipose tissue (epiWAT) or subcutaneous adipose tissue, was observed. Adipose tissue weight and adipocyte area were significantly reduced together with downregulation of adipogenic genes only in the epiWAT. Our findings highlight a distinct effect of MCT1 deficiency in CD8+ T cells in the crosstalk with adipocytes and reinforce the concept that targeting immunometabolic reprogramming in lymphocyte could impact the immune-adipose tissue axis in obesity.
ABSTRACT
Most testicular features undergo major circannual variation in seasonal breeding species. Although the ultimate cause of these variations is known to be the photoperiod in most cases, very little is known about the genetic mechanisms by which these changes are modulated in the testis. Many genes involved in testis development are known to be expressed in the adult testis as well. Since these genes encode genetic regulatory factors, it is reasonable to suspect that they could play some role in the control of the adult testis function. Using immunological detection techniques and RT-Q-PCR, we have studied the spatio-temporal expression pattern of WT1, SF1, SOX9, AMH, and DMRT1 in 4 representative stages of the circannual cycle of the testes of Talpa occidentalis, a mole species with strict seasonal reproduction. AMH is not expressed at any stage of the cycle, showing that inactive adult testes are functionally different from pre-pubertal, juvenile ones. The continuous presence of primary spermatocytes may explain the permanent repression of AMH in the mole testis. WT1 and SF1 are down-regulated and SOX9 is up-regulated in regressed mole testes, suggesting that the modulation of the expression of these genes may be involved in the control of circannual gonad variation. Furthermore, SOX9 and DMRT1 show clear spermatogenic stage-dependent expression patterns. Both genes are expressed more intensely during the proliferative stages of spermatogonia, although SOX9 expression is limited to Sertoli cells, whereas DMRT1 is expressed in both Sertoli and spermatogonial cells. Available data suggest that intratesticular levels of testosterone could regulate circannual spermatogenic variations of seasonal breeders by modulating the expression of DMRT1 to control spermatogonial proliferation.