Browsing by Author "Cortes Mora, Víctor Antonio"

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    Corrigendum: Impact of short and long exposure to cafeteria diet on food intake and white adipose tissue lipolysis mediated by glucagon-like peptide 1 receptor
    (FRONTIERS MEDIA SA, 2023) Mattar, Pamela; Jaque, Cristian; Teske, Jennifer A.; Morselli, Eugenia; Kerr, Bredford; Cortes Mora, Víctor Antonio; Baudrand, Rene; Perez-Leighton, Claudio E. E.
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    Genetics of body composition: From severe obesity to extreme leanness
    (2020) Cortes Mora, Víctor Antonio; Santos Martin, José Luis
    This chapter describes common genetic variations influencing body composition as well as rare mutations causing monogenic obesity or extreme leanness. Large population-based genome-wide association studies (GWAS) revealed more than 500 genetic loci associated with body mass index (BMI) and adiposity traits in the population. Common variations in FTO and MC4R genes are the most statistically consistent signals across studies. Although discoveries of new gene variants through GWAS are important for expanding underlying knowledge on body fat accumulation, their small effect make them insufficient for predicting obesity. Most cases of monogenic obesity are derived from rare mutations in genes belonging to the leptin-melanocortin pathway, such as LEP, LEPR, MC4R, or POMC genes. On the other extreme of BMI, the study of congenital generalized lipodystrophy syndrome has revealed mutations in AGPAT2, BSCL2, PTRF, and CAV1 genes. The evaluation of obesity and leanness as opposite phenotypes represents an interesting approach to assessing causal gene variations related to body composition.
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    Insulin resistance and liver histopathology in metabolically unhealthy subjects do not correlate with the hepatic abundance of NLRP3 inflammasome nor circulating IL-1β levels
    (2021) Quezada Sanhueza, Nicolás; Valencia, Ilse; Torres, Javiera; Maturana, Gregorio; Cerda, Jaime; Arab Verdugo, Juan Pablo; Fuentes, Juan José; Pinto, Claudio; Turiel, Dannae; Cortes Mora, Víctor Antonio
    Introduction Systemic chronic low-grade inflammation has been linked to insulin resistance (IR) and non-alcoholic steatohepatitis (NASH). NOD-like receptor protein 3 (NLRP3) inflammasome and its final product, interleukin (IL)-1 beta, exert detrimental effects on insulin sensitivity and promote liver inflammation in murine models. Evidence linking hepatic NLRP3 inflammasome, systemic IR and NASH has been scarcely explored in humans. Herein, we correlated the hepatic abundance of NLRP3 inflammasome components and IR and NASH in humans.||Research design and methods Metabolically healthy (MH) (n=11) and metabolically unhealthy (MUH) (metabolic syndrome, n=21, and type 2 diabetes, n=14) subjects were recruited. Insulin sensitivity (homeostatic model assessment of IR (HOMA-IR) and Oral Glucose Sensitivity (OGIS(120))), glycemic (glycated hemoglobin), and lipid parameters were determined by standard methods. Plasma cytokines were quantified by Magpix. Hepatic NLRP3 inflammasome components were determined at the mRNA and protein levels by reverse transcription-quantitative PCR and western blot, respectively. Liver damage was assessed by histological analysis (Non-alcoholic Fatty Liver Disease Activity Score (NAS) and Steatosis, Inflammatory Activity, and Fibrosis (SAF) scores). IR and liver histopathology were correlated with NLRP3 inflammasome components as well as with liver and plasma IL-1 beta levels.||Results Body Mass Index, waist circumference, and arterial hypertension frequency were significantly higher in MUH subjects. These patients also had increased high-sensitivity C reactive protein levels compared with MH subjects. No differences in the plasma levels of IL-1 beta nor the hepatic content of Nlrp3, apoptosis-associated speck-like (Asc), Caspase-1, and IL-1 beta were detected between MUH and MH individuals. MUH subjects had significantly higher NAS and SAF scores, indicating more severe liver damage. However, histological severity did not correlate with the hepatic content of NLRP3 inflammasome components nor IL-1 beta levels.||Conclusion Our results suggest that NLRP3 inflammasome activation is linked neither to IR nor to the inflammatory status of the liver in MUH patients.
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    Messenger RNA levels of enzymes involved in glycerolipid synthesis in the brain of the mouse and its alterations in Agpat2-/- and db/db mice
    (2020) González Hodar, Lila Alejandra; Agarwal, Anil K.; Cortes Mora, Víctor Antonio