RESUMEN
As a positional and geometrical isomer of linoleic acid, trans 10, cis 12 conjugated linoleic acid (t10c12-CLA) reduces white fat by reducing food intake, modulating lipid metabolism, and stimulating energy expenditure. However, the t10c12-CLA products are mostly mixtures, making it difficult to obtain accurate results. Studies are needed to investigate the effects of pure t10c12-CLA on animals and humans. In this study, we used the biallelic transgenic (tg) mice, which could produce t10c12-CLA itself, to investigate the effects of pure t10c12-CLA on female reproductive ability. The results showed that the body and relative ovary weights had no significant difference between tg and wild-type (wt) littermates at ages 3 or 10 weeks. While the fecundity test found that tg mice had a significantly longer first litter time (32.0 ± 4.70 days vs. 21.3 ± 2.31 days, P<0.05), and a significantly lower number of litters (4.75 ± 2.75 vs. 6.67 ± 0.57, P<0.05) when compared with wt mice during continuous mating within seven months. Hormone profiles showed that serum estradiol levels did not change in tg mice; however, significantly (P<0.05) decreased progesterone and increased prostaglandin E2 levels were observed in tg mice compared with those of wt mice. Hematoxylin-eosin staining showed no pathological characteristics in tg ovaries, except for the increased atresia follicles (P<0.05). Moreover, the tg mice had a significantly more extended diestrus period than the wt mice (48.4 ± 6.38% vs. 39.6 ± 3.81%, P<0.05). In summary, t10c12-CLA could affect serum progesterone and prostaglandin E2 levels, lead to a disordered estrus cycle, and impact the reproductive performance of female mice. This study provided theoretical and biosafety recommendations for applying t10c12-CLA in female mammals.
RESUMEN
Dietary trans 10, cis 12-conjugated linoleic acid (t10c12-CLA) is a potential candidate in anti-obesity trials. A transgenic mouse was previously successfully established to determine the anti-obesity properties of t10c12-CLA in male mice that could produce endogenous t10c12-CLA. To test whether there is a different impact of t10c12-CLA on lipid metabolism in both sexes, this study investigated the adiposity and metabolic profiles of female Pai mice that exhibited a dose-dependent expression of foreign Pai gene and a shift of t10c12-CLA content in tested tissues. Compared to their gender-match wild-type littermates, Pai mice had no fat reduction but exhibited enhanced lipolysis and thermogenesis by phosphorylated hormone-sensitive lipase and up-regulating uncoupling proteins in brown adipose tissue. Simultaneously, Pai mice showed hepatic steatosis and hypertriglyceridemia by decreasing gene expression involved in lipid and glucose metabolism. Further investigations revealed that t10c10-CLA induced excessive prostaglandin E2, adrenaline, corticosterone, glucagon and inflammatory factors in a dose-dependent manner, resulting in less heat release and oxygen consumption in Pai mice. Moreover, fibroblast growth factor 21 overproduction only in monoallelic Pai/wt mice indicates that it was sensitive to low doses of t10c12-CLA. These results suggest that chronic t10c12-CLA has system-wide effects on female health via synergistic actions of various hormones.
Asunto(s)
Corticosterona , Dinoprostona , Epinefrina , Factores de Crecimiento de Fibroblastos , Glucagón , Ácidos Linoleicos Conjugados , Ratones Transgénicos , Animales , Femenino , Factores de Crecimiento de Fibroblastos/metabolismo , Factores de Crecimiento de Fibroblastos/genética , Ratones , Ácidos Linoleicos Conjugados/farmacología , Ácidos Linoleicos Conjugados/metabolismo , Corticosterona/metabolismo , Dinoprostona/metabolismo , Glucagón/metabolismo , Epinefrina/metabolismo , Termogénesis/efectos de los fármacos , Termogénesis/genética , Masculino , Metabolismo de los Lípidos/efectos de los fármacos , Tejido Adiposo Pardo/metabolismo , Tejido Adiposo Pardo/efectos de los fármacos , Hígado Graso/metabolismo , Hígado Graso/genética , Lipólisis/efectos de los fármacos , Hipertrigliceridemia/metabolismo , Hipertrigliceridemia/genética , Adiposidad/efectos de los fármacosRESUMEN
Currently, the relationship between nutritional indices and the prognosis of hepatocellular carcinoma (HCC) patients treated with immune checkpoint inhibitors (ICIs) and tyrosine kinase inhibitors (TKIs) remains unclear. This study aims to investigate the prognostic value of psoas muscle index (PMI), prognostic nutritional index (PNI), body mass index (BMI), and geriatric nutritional risk index (GNRI) in HCC patients treated with ICIs combined with TKIs. A total of 124 male patients with HCC were included in this study. PNI, PMI, BMI, and GNRI were calculated at the beginning of treatment. The Cox proportional hazards model was used to analyze the effect of various variables. In the univariate analysis, PMI, PNI, GNRI, and ALB were found to impact the outcomes of the patients at different follow-up times. However, the predictive value of these nutritional indices was eliminated when established risk factors were considered. In the multivariate analysis that only included nutrition-related indicators, PMI emerged as an independent prognostic factor for 1-year treatment outcomes. The group with low PMI (≤5.5409 cm2/m2) was found to have a higher risk of death at one year and at the end of the follow-up period.
Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Masculino , Anciano , Pronóstico , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Carcinoma Hepatocelular/tratamiento farmacológico , Músculos Psoas/diagnóstico por imagen , Neoplasias Hepáticas/tratamiento farmacológicoRESUMEN
Trans 10, cis 12-conjugated linoleic acid (t10c12-CLA) from ruminant-derived foodstuffs can induce body fat loss after oral administration. In the current study, a transgenic mouse that produced t10c12-CLA had been generated by inserting the Propionibacterium acnes isomerase (Pai) expression cassette into the Rosa26 locus, and its male offspring were used to elucidate the enduring influence of t10c12-CLA on overall health. Compared to their wild-type (wt) C57BL/6J littermates, both biallelic Pai/Pai and monoallelic Pai/wt mice exhibited reduced plasma triglycerides levels, and Pai/wt mice exclusively showed increased serum fibroblast growth factor 21. Further analysis of Pai/Pai mice found a decrease in white fat and an increase in brown fat, with more heat release and less physical activity. Analysis of Pai/Pai brown adipose tissues revealed that hyperthermia was associated with the over-expression of carnitine palmitoyltransferase 1B, uncoupling proteins 1 and 2. These findings suggest that the systemic and long-term impact of t10c12-CLA on obesity might be mediated through the pathway of fibroblast growth factor 21 when low doses are administered or through enhanced thermogenesis of brown adipose tissues when high doses are employed.