Herrero, I. (Ignacio)

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    Factors related to increased resting energy expenditure in men with liver cirrhosis
    (2016) Prieto-Frías, C. (Cesár); Conchillo, M. (M.); Payeras, M. (Marina); Iñarrairaegui, M. (Mercedes); D'Avola, D. (Delia); Frühbeck, G. (Gema); Salvador, J. (Javier); Rodriguez, M. (Macarena); Richter, J.A. (José Ángel); Mugueta, C. (Carmen); Gil-Maria, J. (Jesús); Herrero, I. (Ignacio); Prieto, J. (Jesús); Sangro, B. (Bruno); Quiroga, J. (Jorge)
    Objective Hypermetabolism in cirrhosis is associated with a high risk of complications and mortality. However, studies about underlying mechanisms are usually focussed on isolated potential determinants and specific etiologies, with contradictory results. We aimed at investigating differences in nutrition, metabolic hormones, and hepatic function between hypermetabolic and nonhypermetabolic men with cirrhosis of the liver. Patients and methods We prospectively enrolled 48 male cirrhotic inpatients. We evaluated their resting energy expenditure (REE) and substrate utilization by indirect calorimetry, body composition by dual-energy X-ray absorptiometry, liver function, and levels of major hormones involved in energy metabolism by serum sample tests. Patients with ascites, specific metabolic disturbances, and hepatocellular carcinoma were excluded. Results REE and REE adjusted per fat-free mass (FFM) were significantly increased in cirrhotic patients. Overall, 58.3% of cirrhotic patients were classified as hypermetabolic. Groups did not differ significantly in age, etiology of cirrhosis, liver function, presence of ascites, use of diuretics, β-blockers, or presence of transjugular intrahepatic portosystemic shunts. Hypermetabolic cirrhotic patients had lower weight, BMI (P< 0.05), nonprotein respiratory quotient (P< 0.01), leptin (P<0.05), and leptin adjusted per fat mass (FM) (P<0.05), but higher FFM% (P< 0.05) and insulin resistance [homeostatic model assessment-insulin resistance (HOMA-IR)] (P<0.05). Only HOMA-IR, leptin/FM, and FFM% were independently related to the presence of hypermetabolism. Conclusion Hypermetabolic cirrhotic men are characterized by lower weight, higher FFM%, insulin resistance, and lower leptin/FM when compared with nonhypermetabolic men. HOMA-IR, FFM%, and leptin/FM were independently associated with hypermetabolism, and may serve as easily detectable markers of this condition in daily clinical practice
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    New insights into the regulation of bile acids synthesis during the early stages of liver regeneration: A human and experimental study
    (Elsevier B.V., 2024) Latasa, M.U. (María Ujué); Lopez-Pascual, A. (Amaya); Corrales, F.J. (Fernando José); Lucena-Ramírez, J.F. (Juan Felipe); Berasain, C. (Carmen); Arechederra, M. (María); Rotellar, F. (Fernando); Fernández-Barrena, M.G. (Maite G.); Pardo, F. (Fernando); Uriarte, I. (Iker); Irigaray-Miramon, A. (Ainara); Avila, M.A. (Matías Antonio); Sangro, B. (Bruno); Basualdo, J. (Jorge); Monte, M.J. (María J.); Herranz, J.M. (José M.); Merlen, G. (Gregory); Santamaría, E. (Eva); Tordjmann, T. (Thierry); Adán-Villaescusa, E. (Elena); Herrero, I. (Ignacio); Rainteau, D. (Dominique); Argemí, J. (Josepmaria); Marin, J.J.G (Jose J.G.)
    Background and aims: Liver regeneration is essential for the preservation of homeostasis and survival. Bile acids (BAs)-mediated signaling is necessary for liver regeneration, but BAs levels need to be carefully controlled to avoid hepatotoxicity. We studied the early response of the BAs-fibroblast growth factor 19 (FGF19) axis in healthy individuals undergoing hepatectomy for living donor liver transplant. We also evaluated BAs synthesis in mice upon partial hepatectomy (PH) and acute inflammation, focusing on the regulation of cytochrome-7A1 (CYP7A1), a key enzyme in BAs synthesis from cholesterol. Methods: Serum was obtained from twelve human liver donors. Mice underwent 2/3-PH or sham-operation. Acute inflammation was induced with bacterial lipopolysaccharide (LPS) in mice fed control or antoxidant-supplemented diets. BAs and 7α-hydroxy-4-cholesten-3-one (C4) levels were measured by HPLC-MS/MS; serum FGF19 by ELISA. Gene expression and protein levels were analyzed by RT-qPCR and western-blot. Results: Serum BAs levels increased after PH. In patients with more pronounced hypercholanemia, FGF19 concentrations transiently rose, while C4 levels (a readout of CYP7A1 activity) dropped 2 h post-resection in all cases. Serum BAs and C4 followed the same pattern in mice 1 h after PH, but C4 levels also dropped in shamoperated and LPS-treated animals, without marked changes in CYP7A1 protein levels. LPS-induced serum C4 decline was attenuated in mice fed an antioxidant-supplemented diet. Conclusions: In human liver regeneration FGF19 upregulation may constitute a protective response from BAs excess during liver regeneration. Our findings suggest the existence of post-translational mechanisms regulating CYP7A1 activity, and therefore BAs synthesis, independent from CYP7A1/Cyp7a1 gene transcription.