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Ovarian senescence increases liver fibrosis in humans and zebrafish with steatosis.

Turola E, Petta S, Vanni E, Milosa F, Valenti L, Critelli R, Miele L, Maccio L, Calvaruso V, Fracanzani AL, Bianchini M, Raos N, Bugianesi E, Mercorella S, Di Giovanni M, Craxì A, Fargion S, Grieco A, Cammà C, Cotelli F, Villa E - Dis Model Mech (2015)

Bottom Line: In the entire cohort, at multivariate logistic regression, male gender [odds ratio (OR): 1.408, 95% confidence interval (95% CI): 0.779-2.542, P=0.25] vs women at reproductive age was not associated with F2-F4 fibrosis, whereas a trend was observed for menopause (OR: 1.752, 95% CI: 0.956-3.208, P=0.06).In women, menopause (OR: 2.717, 95% CI: 1.020-7.237, P=0.04) was independently associated with F2-F4 fibrosis.Similarly, in overfed zebrafish, old female fish with failing ovarian function [as demonstrated by extremely low circulating estradiol levels (1.4±0.1 pg/µl) and prevailing presence of atretic follicles in the ovaries] developed massive steatosis and substantial fibrosis (comparable with that occurring in males), whereas young female fish developed less steatosis and were totally protected from the development of fibrosis.

View Article: PubMed Central - PubMed

Affiliation: Gastroenterology Unit, Department of Internal Medicine, University of Modena and Reggio Emilia, 41124 Modena, Italy.

No MeSH data available.


Related in: MedlinePlus

RT-qPCR analysis for the expression of marker genes in the livers of overfed zebrafish. Genes involved in lipid metabolism (A-D), inflammation (E) and fibrosis (F) in zebrafish. Samples from five fish per subgroup were analyzed. Gene expression was reported as the calibrated normalized relative quantity (CNRQ) geometric mean±s.e.m. of each group expressed as log(2). Each value was normalized to the CNRQ geometric mean of the corresponding control.
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DMM019950F4: RT-qPCR analysis for the expression of marker genes in the livers of overfed zebrafish. Genes involved in lipid metabolism (A-D), inflammation (E) and fibrosis (F) in zebrafish. Samples from five fish per subgroup were analyzed. Gene expression was reported as the calibrated normalized relative quantity (CNRQ) geometric mean±s.e.m. of each group expressed as log(2). Each value was normalized to the CNRQ geometric mean of the corresponding control.

Mentions: To investigate the mechanisms underlying the development and progression of liver damage in obesity-associated conditions, we analyzed the expression of marker genes involved in lipid metabolism (pparg, ppara and sreb1c), hepatic lipogenesis and fatty acid oxidation (creb3l3), inflammation (il6) and fibrosis (tgfb) (Fig. 4). Quantitative real-time PCR (RT-qPCR) analyses showed increased transcript levels for pparg and srebp1c, and decreased creb3l3 transcript levels at weeks 6 and 16 in all groups but young females, in which the reverse occurred (Fig. 4A,B,D). Upregulation of ppara was observed in all groups as compared with controls. However, in young females, the levels of ppara mRNA were significantly lower as compared with that of all the other groups (Fig. 4C). Increased expression of the il6 transcript was found in males and old females from week 6, and in old males at week 16. In young females, il6 was downregulated at all time points (Fig. 4E). tgfb showed an increased expression in older animals from week 1, as compared with basal levels. In young animals (both males and females), tgfb expression was mostly downregulated (Fig. 4F).Fig. 4.


Ovarian senescence increases liver fibrosis in humans and zebrafish with steatosis.

Turola E, Petta S, Vanni E, Milosa F, Valenti L, Critelli R, Miele L, Maccio L, Calvaruso V, Fracanzani AL, Bianchini M, Raos N, Bugianesi E, Mercorella S, Di Giovanni M, Craxì A, Fargion S, Grieco A, Cammà C, Cotelli F, Villa E - Dis Model Mech (2015)

RT-qPCR analysis for the expression of marker genes in the livers of overfed zebrafish. Genes involved in lipid metabolism (A-D), inflammation (E) and fibrosis (F) in zebrafish. Samples from five fish per subgroup were analyzed. Gene expression was reported as the calibrated normalized relative quantity (CNRQ) geometric mean±s.e.m. of each group expressed as log(2). Each value was normalized to the CNRQ geometric mean of the corresponding control.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4582103&req=5

DMM019950F4: RT-qPCR analysis for the expression of marker genes in the livers of overfed zebrafish. Genes involved in lipid metabolism (A-D), inflammation (E) and fibrosis (F) in zebrafish. Samples from five fish per subgroup were analyzed. Gene expression was reported as the calibrated normalized relative quantity (CNRQ) geometric mean±s.e.m. of each group expressed as log(2). Each value was normalized to the CNRQ geometric mean of the corresponding control.
Mentions: To investigate the mechanisms underlying the development and progression of liver damage in obesity-associated conditions, we analyzed the expression of marker genes involved in lipid metabolism (pparg, ppara and sreb1c), hepatic lipogenesis and fatty acid oxidation (creb3l3), inflammation (il6) and fibrosis (tgfb) (Fig. 4). Quantitative real-time PCR (RT-qPCR) analyses showed increased transcript levels for pparg and srebp1c, and decreased creb3l3 transcript levels at weeks 6 and 16 in all groups but young females, in which the reverse occurred (Fig. 4A,B,D). Upregulation of ppara was observed in all groups as compared with controls. However, in young females, the levels of ppara mRNA were significantly lower as compared with that of all the other groups (Fig. 4C). Increased expression of the il6 transcript was found in males and old females from week 6, and in old males at week 16. In young females, il6 was downregulated at all time points (Fig. 4E). tgfb showed an increased expression in older animals from week 1, as compared with basal levels. In young animals (both males and females), tgfb expression was mostly downregulated (Fig. 4F).Fig. 4.

Bottom Line: In the entire cohort, at multivariate logistic regression, male gender [odds ratio (OR): 1.408, 95% confidence interval (95% CI): 0.779-2.542, P=0.25] vs women at reproductive age was not associated with F2-F4 fibrosis, whereas a trend was observed for menopause (OR: 1.752, 95% CI: 0.956-3.208, P=0.06).In women, menopause (OR: 2.717, 95% CI: 1.020-7.237, P=0.04) was independently associated with F2-F4 fibrosis.Similarly, in overfed zebrafish, old female fish with failing ovarian function [as demonstrated by extremely low circulating estradiol levels (1.4±0.1 pg/µl) and prevailing presence of atretic follicles in the ovaries] developed massive steatosis and substantial fibrosis (comparable with that occurring in males), whereas young female fish developed less steatosis and were totally protected from the development of fibrosis.

View Article: PubMed Central - PubMed

Affiliation: Gastroenterology Unit, Department of Internal Medicine, University of Modena and Reggio Emilia, 41124 Modena, Italy.

No MeSH data available.


Related in: MedlinePlus