Loss-of-function genetic screens are a powerful approach to identify the genes involved in biological processes. For nearly a century, forward genetic screens in model organisms have provided enormous insight into many cellular processes. However, the difficulty in generating and recovering bi-allelic mutations in diploid cells severely hindered the performance of forward genetic screens in mammalian cells. The development of a retroviral gene-trap vector to mutagenise the human near-haploid KBM7 cell line transformed forward genetic screens in human cells. The re-purposing of the microbial CRISPR/Cas9 system now offers an effective method to generate gene knockouts in diploid cells. Here, I performed a head-to-head comparison of retroviral gene-trap mutagenesis screens and genome-wide CRISPR knockout screens in KBM7 cells. The two screening approaches were equally effective at identifying genes required for the endoplasmic reticulum (ER)-associated degradation of MHC class I molecules. The ER-resident enzyme HMG-CoA reductase (HMGCR) catalyses the rate-limiting step in the cholesterol biosynthesis pathway and is targeted therapeutically by statins. To maintain cholesterol homeostasis, the expression of HMGCR is tightly regulated by sterols transcriptionally and post-translationally. Sterols induce the association of HMGCR with Insig proteins, which recruit E3 ubiquitin ligase complexes to mediate degradation of HMGCR by the ubiquitin proteasome system. However, the identity of the E3 ligase(s) responsible for HMGCR ubiquitination is controversial. Here, I use a series of genome-wide CRISPR knockout screens using a fluorescently-tagged HMGCR exogenous reporter and an endogenous HMGCR knock-in as an unbiased approach to identify the E3 ligases and any additional components required for HMGCR degradation. The CRISPR screens identified a role for the poorly characterised ERAD E3 ligase RNF145. I found RNF145 to be functionally redundant with gp78, an E3 ligase previously implicated in HMGCR degradation, and the loss of both E3 ligases was required to significantly inhibit the sterol-induced degradation and ubiquitination of HMGCR. A focused E3 ligase CRISPR screen revealed that the combined loss of gp78, RNF145 and Hrd1 was required to completely block the sterol-induced degradation of HMGCR. I present a model to account for this apparent complexity.

No description available.

Selenium (Se) is an essential mineral with functions for both animals and humans. There are several regions in the world deficient in this mineral and studies have related Se supplemented with reducing cholesterol. Thus, the objective of this study was to evaluate the Se effect in different levels and sources in the diet finishing of Nellore cattle on the performance and meat quality. It was used 63 Nellore cattle (412 kg and ± 24 months of age) in a completely randomized design with two sources (sodium selenite and selenium-enriched yeast) and four supplementation levels (0; 0.3; 0.9 and 2.7 mg Se/kg DM). There were no changes in performance and carcass characteristics. The Se level reduced (P<0.01) lipid and proteins oxidation (TBARS and carbonyl) compared to the control treatment on retail display storage (0, 2, 4 and 6 days). Organic Se, regardless of level, provided Se 138% higher (P<0.0001) in meat and 22.6% higher (P<0.0001) in serum than inorganic Se. The activity of glutathione peroxides (GPx) in muscle was 288% higher for animals supplemented with selenium and consequently, the cholesterol concentration in L. dorsi was 10.2% lower (P<0.001). The serum HMG-CoA reductase concentration was 32.7% lower in animals receiving Se supplementation (organic or inorganic). In conclusion, Se supplementation in beef cattle diet is a way of naturally producing selenium-enriched meat and with better quality for human consumption. / O selênio (Se) é um mineral essencial com funções para animais e humanos. Existem várias regiões do mundo deficientes neste mineral e estudos têm relacionado a suplementação de Se com a redução do colesterol. Assim, o objetivo deste estudo foi avaliar o efeito de diferentes teores e fontes de Se na dieta de terminação de bovinos Nelore sobre o desempenho e a qualidade da carne. Foram utilizados 63 animais da raça Nelore (412 kg e ± 24 meses de idade) em delineamento inteiramente casualizado, com duas fontes (selenito de sódio e selênio levedura) e quatro teores de suplementação (0; 0,3; 0,9 e 2,7 mg Se/kg MS) em confinamento, durante 84 dias. Não houve alterações no desempenho e nas características de carcaça. O teor de Se reduziu (P <0,01) a oxidação lipídica e proteica (TBARS e carbonila) em comparação ao tratamento controle durante o armazenamento em simulação de exposição no varejo (0, 2, 4 e 6 dias). O Se orgânico, independentemente do teor, forneceu valor de Se 138% superior (P <0,0001) na carne e 22,6% superior (P <0,0001) no soro em relação ao Se inorgânico. A atividade glutationa peroxidase (GPx) no músculo foi 288% maior nos animais suplementados com selênio e, consequentemente, a concentração de colesterol na carne foi 10,2% menor (P <0,001). A concentração sérica de HMG-CoA redutase foi 32,7% menor nos animais que receberam suplementação de Se (orgânico ou inorgânico). Foi concluído que a suplementação com Se na dieta de bovinos de corte é uma forma de produzir carnes enriquecidas com selênio naturalmente e com melhor qualidade para consumo humano.

HMGN Proteine sind Architekturelemente des Chromatins und besitzen die Fähigkeit, Chromatin aufzulockern. Sie ermöglichen anderen Proteinen den Zugang zu Nukleosomen und unterstützen DNA-abhängige Prozesse wie Replikation, Transkription und DNA-Reparatur. In dieser Arbeit wurde die funktionelle Rolle der HMGN Proteine während der Embryogenese am Beispiel des südafrikanischen Krallenfroschs Xenopus laevis untersucht. Dabei wurde entdeckt, dass sowohl die Expression als auch die zelluläre Verteilung der HMGN Proteine entwicklungsspezifisch reguliert ist. Eine Manipulation der HMGN Proteinmengen während der Embryonalentwicklung führte zu schweren Fehlentwicklungen in Postblastula Embryonen. In der Oogenese waren sowohl Xenopus HMGN mRNAs als auch Xenopus HMGN Proteine in allen Oozytenstadien nachweisbar. Interessanterweise waren HMGN Proteine in späteren Oozytenstadien nur im Zytoplasma zu finden und nicht mit Lampenbürstenchromosomen assoziiert. Im Zuge der Maturation der Oozyten zu Eiern verschwinden die Proteine gänzlich. Während der Embryogenese waren HMGN Proteine dann erst wieder ab der Blastula detektierbar, zeitgleich mit der transkriptionellen Aktivierung des embryonalen Genoms. Gleichzeitig wiesen ihre Expressionsmuster, zumindest auf mRNA-Ebene, auf Gewebspezifität hin. Whole mount in situ-Hybridisierungen und RT-PCR-Analysen zeigten eine erhöhte mRNA-Menge in mesodermalen und neuroektodermalen Geweben von Schwanzknospenstadien. Nach Injektion rekombinanter HMGN Proteine (Überexpression) oder Morpholino-Antisense-Oligonukleotiden (knock-down) in die Zygote entwickelten sich Embryonen mit offenen Rücken, stark verkürzten und gebogenen Körperachsen und deformierten Kopfstrukturen als Hauptmerkmale. Histologische Analysen und insbesondere die Magnetresonanz Bildgebung deuteten auf Fehler in der Mesodermdifferenzierung hin. Die Analysen zeigen, dass eine bestimmte kritische zelluläre HMGN Proteinmenge für eine korrekte Embryonalentwicklung von Xenopus laevis notwendig ist. Durch „animal cap assays“ und RT-PCR-Expressionsanalysen Mesoderm-spezifischer Gene konnte schließlich gezeigt werden, dass HMGN Proteine die Regulation Mesoderm-spezifischer Gene beeinflussen. Die Ergebnisse lassen vermuten, dass auch die HMGN-Genexpression während der Mesodermdifferenzierung reguliert wird. Durch eine Analyse des Expressionsbeginns entwicklungsrelevanter Gene während der Midblastula Transition konnte gezeigt werden, dass veränderte HMGN Proteinmengen den Expressionsbeginn spezifischer Gene wie Xbra und chordin beeinflussen. Damit konnte zum ersten Mal ein Einfluss dieser ubiquitären Chromatinproteine auf die Expression spezifischer Gene gefunden werden. Die durch HMGN Proteine verursachte fehlerhafte Expression von Xbra und chordin als Schlüsselgene der Mesodermdifferenzierung kann die Fehlentwicklungen mesodermaler Strukturen erklären. / HMGN proteins are architectural chromatin proteins that reduce the compaction of the chromatin fiber, facilitate access to nucleosomes and modulate DNA-dependent processes such as replication, transcription and DNA repair. In this work the functional role of the HMGN proteins during embryogenesis was analyzed using the African clawed frog Xenopus laevis as a model system. The expression and cellular location of the HMGN proteins was found to be developmentally regulated. Experimental manipulations of the HMGN protein amounts led to gross developmental defects in postblastula embryos. HMGN transcripts and proteins were present throughout oogenesis. Interestingly, the HMGN proteins were stored in the cytoplasm of later oocyte stages and excluded from the oocytes nuclei and lampbrush chromosomes. Upon maturation of oocytes into eggs, HMGN proteins were no longer detectable. During embryogenesis, HMGN proteins were first detected in blastula stage embryos, coinciding with the transcriptional activation of the embryonic genome. At least at the mRNA level the expression pattern showed a tissue specific pattern, with relatively high levels of mRNAs in the mesodermal and neuroectodermal regions of early tailbud embryos as shown by whole mount in-situ hybridization and RT-PCR-analyses. After microinjection of recombinant HMGN proteins (overexpression) or morpholino-antisense oligonucleotides (knock-down) the embryos displayed typical phenotypes with imperfect closure of the blastopore, distorted body axis and abnormal head structures. Histological analyses and magnetic resonance imaging indicated that mesoderm differentiation was particularly affected by aberrant HMGN protein levels. The results demonstrate that proper embryonic development of Xenopus laevis requires precisely regulated levels of HMGN proteins. “Animal cap assays” and RT-PCR-analyses of the expression of mesodermal genes indicated that HMGN proteins are involved in the regulation of mesoderm specific genes. These experiments also indicated that the HMGN expression itself is regulated during mesoderm differentiation. Moreover, by studying the expression pattern of developmentally relevant genes during midblastula transition it became evident that altered HMGN protein levels influence the onset of the expression of specific genes such as Xbra and chordin. The results show, for the first time, that these ubiquitous chromatin proteins modulate the expression of specific genes. The HMGN-induced misexpression of Xbra and chordin as key regulatory genes during mesoderm differentiation may explain the observed malformations of mesodermal structures.

L'enzim HMG-CoA reductasa (HMGR) catalitza la primera etapa limitant en la síntesi d'isoprenoides citosòlics. En plantes, és un enzim de membrana i la seva primera destinació subcel·lular és el reticle endoplasmàtic. Estructuralment, està formada per un domini amino-terminal (que inclou una regió amino-terminal citosòlica i dos fragments transmembrana) i un domini catalític altament conservat en tota l'escala evolutiva. En totes les espècies de plantes conegudes fins al moment, existeixen isoformes de l'HMGR codificades per diferents gens. Concretament, en Arabidopsis thaliana el gen hmg1 (expressat de forma majoritària) codifica per a les isoformes HMGR1S i HMGR1L, i el gen hmg2 (expressat a arrels, plàntules i inflorescències) codifica per a la isoforma HMGR2. A nivell d'estructura primària l'HMGR1L difereix de l'HMGR1S per la presència d'una regió extra de 50 residus aminoacídics a l'extrem amino-terminal. El domini amino-terminal confereix diferents destinacions de localització subcel·lular a la proteïna. En un treball anterior, es van identificar tres proteïnes que interaccionen amb les isoformes derivades del gen hmg1: AtB"α, AtB"β i AtKLC-1. Les dues primeres interaccionen específicament amb la regió amino-terminal de les isoformes HMGR1S i HMGR1L. Les proteïnes AtB"α i AtB"β són isoformes de la subunitat B" reguladora del complex proteïna fosfatasa 2A (PP2A). En el genoma d'A. thaliana hi ha cinc seqüències que codifiquen per a isoformes de la subunitat B" que comparteixen una gran homologia. En l'estructura primària de la subunitat B" s'han identificat motius EF-Hand (implicats en la unió a calci). S'ha demostrat que tant AtB"α com AtB"β uneixen calci. La tercera proteïna identificada, AtKLC-1, interacciona específicament amb la regió amino-terminal de l'HMGR1L. S'ha determinat per assaigs de doble híbrid en llevat i, posteriorment confirmats in vitro, que la PR65, proteïna estructural del complex PP2A, interacciona específicament amb l'AtKLC-1. La regió de la PR65 suficient per a la interacció amb la subunitat B" reguladora, AtB"α, i amb l'AtKLC-1 comprèn la mateixa seqüència aminoacídica. Per tant, l'AtB"α i l'AtKLC-1 podrien competir per a l'associació amb la PR65. Així, en la cèl·lula, la PP2A podria regular d'una forma particular les isoformes HMGR1S i HMGR1L. Assaigs in vivo i in vitro demostren que la PP2A és un regulador negatiu de l'enzim HMGR. Els ions calci inhibeixen també l'activitat HMGR. Per a què es dugui a terme la repressió de l'activitat HMGR tant per calci com per PP2A, es requereix el domini amino-terminal de la proteïna. Per tant, els resultats són consistents amb què les subunitats AtB" i/o AtKLC-1 duen a terme un paper mediador en la modulació de l'HMGR per la PP2A. El domini amino-terminal de l'HMGR1S està implicat en la morfogènesi de vesícules derivades del reticle endoplasmàtic. La subunitat AtB"α i la resta del complex PP2A participen en aquest procés. El domini amino-terminal de l'HMGR1L dirigeix la proteïna a la trama de reticle endoplasmàtic. La PP2A participa també en la localització subcel·lular d'aquesta isoforma.S'ha caracteritzat una línia mutant en el gen hmg1 d'A. thaliana que mostra absència del transcrit hmg1 i una reduïda activitat HMGR. Les plantes d'aquest mutant creixen normalment en un medi de cultiu estèril i manifesten severes alteracions del desenvolupament quan són cultivades en terra. L'addició de mevalonat, producte de la reacció catalitzada per l'HMGR, no reverteix el fenotip. Les dades indiquen que el gen hmg1 duu a terme una funció no metabòlica relacionada amb l'adaptació al medi. En aquestes condicions de creixement, les estructures vesiculars induïdes per l'HMGR1S podrien tenir alguna funció essencial relacionada amb la resposta a estrès. / "ROLE OF THE PROTEINS AtKLC-1 AND AtB" IN THE REGULATION OF HMG-CoA REDUCTASE IN ARABIDOPSIS THALIANA".TEXT: The enzyme HMG-CoA reductase (HMGR) catalyses the formation of mevalonate in the first rate-limiting step of the mevalonate pathway for isoprenoid biosynthesis. All known plant HMGR isoforms are primarily targeted to the endoplasmic reticulum (ER).These proteins contain two domains: an N-terminal domain (which includes an N-terminal cytosolic region and two membrane-spanning sequences) and a conserved catalytic domain. In all plant species, there are a variety of HMGR isoforms encoded by a multigene family. In Arabidopsis thaliana, two genes (hmg1 and hmg2) encode three HMGR isoforms (HMGR1S, HMGR1L and HMGR2). Isoforms HMGR1S and HMGR1L are identical in sequence but HMGR1L is extended 50 amino acid residues at the N-terminal end. In a previous study, three proteins had been identified which specifically interact with the HMGR1L N-terminal end. Two of these proteins, designed AtB" and AtB", are regulatory B" subunits of protein phosphatase 2A (PP2A). They bind the N-terminal region of HMGR1S and HMGR1L. The third one, AtKLC-1, exclusively interact with the N-terminal region of HMGR1L. In vitro assays have revealed that PR65, PP2A scaffolding subunit, specifically interact with AtKLC-1. Genetic and pharmacological approaches demonstrate that PP2A exerts an inhibitory control over HMGR. These results indicate that AtB" or AtKLC-1 could have a mediating role in the HMGR regulation carried out by PP2A. The N-terminal domain of the HMGR1S isoform is involved in the biogenesis of vesicle structures derived from the ER membranes. The PP2A complex is concerned in this process and the subunit AtB" acts as an interceding factor. Furthermore, we have characterized an Arabidopsis thaliana insertion mutant for hmg1. This mutant exhibits no visible phenotype under sterile growth conditions but shows dwarfing and sterility when it is grown in a soil substrate. The addition of mevalonate doesn't rescue this phenotype. These data suggest that hmg1 performs a no-metabolic function related with environment adaptation. In this context, ER derived vesicles induced by HMGR1S could play an essential role related with stress response.

Thesis (Ph.D. in Molecular Biology) -- University of Colorado at Denver and Health Sciences Center, 2005. / Typescript. Includes bibliographical references (leaves 165-185). Free to UCDHSC affiliates. Online version available via ProQuest Digital Dissertations;

Class of 2012 Abstract / Specific Aims: To evaluate the quality of evidence in the literature substantiating major drug-drug interactions of the HMG-CoA reductase inhibitors (statins) atorvastatin, lovastatin, and simvastatin with the azole anti-fungals fluconazole, itraconazole, and ketoconazole. Methods: In this descriptive retrospective analysis, a list of articles reporting on each drug-drug interaction was compiled from the online databases Medline and International Pharmaceutical Abstracts, and the drug compendia Micromedex and Facts & Comparisons. The studies included in this analysis were primary literature reports, written in English, and consisted of human subjects. All studies included were evaluated using a 5-point quality of evidence scale developed to assess drug-drug interactions (van Roon scale). This scale rates the study type from lowest to highest quality, from zero to four. Case reports were additionally analyzed using the Drug Interaction Probability Scale (DIPS). The DIPS tool uses 10 questions to evaluate the probability that an adverse event is caused by a drug-drug interaction. Main Results: Twenty-one studies met the selection criteria. There were three studies involving atorvastatin, four studies involving lovastatin, and fourteen studies involving simvastatin. The mean quality of evidence score on the van Roon scale was 2.0 + 0.77, where atorvastatin studies had a score of 2.3 + 1.15, lovastatin had a score of 2.25 + 0.95 and simvastatin had a score of 1.86 + 0.66. Seventy-one percent of the studies reviewed were case reports. Conclusions: The reports substantiating some drug-drug interactions may be of little and low quality evidence.

In February 2012, the FDA issued safety label changes and monitoring requirements for statin therapy. A risk of cognitive impairment was noted, although evidence was largely based on observational data, including case reports. In 2014, the National Lipid Association's safety task force found that evidence does not support cognitive decline as a classwide effect for statins. Some evidence has shown that statins may actually have beneficial effects on cognition. This article discusses management of statin therapy in patients with cardiovascular risk who may experience cognitive decline or have cognitive impairment, such as Alzheimer disease.

HMG-CoA reductase inhibitors, known commonly as statins are one of the most widely prescribed medications worldwide. Statins reduce circulating cholesterol levels and are very effective at reducing one’s risk for all-cause and cardiovascular mortality. Though generally well tolerated, statin-associated muscle symptoms (SAMS) present in more than a quarter of statin users. The most common SAMS is myalgia or muscle pain. Statin myalgia often presents in the absence of myofibre damage, making its origin and treatment ambiguous. There are numerous rodent models for statin myopathy in the literature, but surprisingly there is no representation of statin myalgia that we are aware of. This is shocking given the high prevalence of statin myalgia compared to statin myopathy. Recently, our lab published an in vitro model of statin myalgia that focused on elevated xCT transporter activity and interstitial glutamate. This model explains that pain perceived in statin myalgia is the result of statins’ downstream ability to elevate skeletal muscle interstitial glutamate concentrations, thereby activating peripheral nociceptors. The studies herein aimed to create an in vivo rodent model of statin myalgia based on the aforementioned in vitro model. We hypothesized that glutamate, sampled by way of skeletal muscle microdialysis, would be elevated in the skeletal muscle interstitium of rats following statin treatment. Drawing conclusions on the role of glutamate in statin myalgia was not a straightforward process and required multiple model adjustments due to confounding variables. Additionally, many of the recognized effects of statins that were assumed from human and in vitro studies did not translate well to our rodent model. This was the first attempt at creating an in vivo model of statin myalgia and evidence suggests that a rodent model may not be an appropriate representation of what occurs in humans. While these studies also raised doubt on the efficacy of rodent models for SAMS investigations in general and highlighted the importance of having standardized models, certain limitations and assumptions of our model must be addressed before concrete conclusions can be drawn. / Thesis / Master of Science in Medical Sciences (MSMS) / Statins, a class of cholesterol-lowering medications, are one of the most widely prescribed medications worldwide. They have been demonstrated to be very effective at reducing one’s risk of cardiovascular-related death. Statins are generally very well tolerated, however, the most common negative side effects of their use are muscle related and include muscle pain, muscle inflammation and muscle damage. Muscle pain is the most common of these symptoms to present and interestingly, often presents without any clinical indication of muscle damage. The lack of a physical explanation for what is causing this pain makes treating statin-associated muscle pain quite difficult. A lot of effort has gone into determining the mechanism(s) for statin-associated muscle damage, however, there is a gap when it comes to investigating the mechanism(s) for statin-associated muscle pain. The studies herein, therefore, aimed to bridge this gap and investigated a potential mechanism for statin-associated muscle pain in a rodent model. The foundation for this model was built on a cell culture model that was previously developed in our lab. Our data suggest that a rodent model for statin-associated muscle pain may not be an appropriate representation of what occurs in humans. In particular, reduced blood cholesterol and substantial skeletal muscle oxidative stress were not demonstrated in our model as they have been in humans and in cell culture studies. This raised concern around the efficacy of rodent models for statin associated muscle symptoms in general and highlighted the importance of having standardized models. The differences between human/cell culture studies and rodent models also made it difficult to draw firm conclusions on whether the mechanism for statin myalgia investigated herein is supported.

Introdução: Atualmente as Doenças Crônicas não Transmissíveis (DCNTs) são um dos maiores problemas de saúde pública da sociedade. É bastante claro o papel da dieta no controle do colesterol e na incidência de doenças cardiovasculares. Neste sentido, o amaranto desperta grande interesse devido a sua propriedade hipocolesterolemizante. Estudos sugerem que seu efeito hipocolesterolemizante está associado à inibição da enzima HMG-CoA redutase, chave na síntese do colesterol endógeno. Objetivo: Avaliar a atividade enzimática hepática da HMG-CoA redutase de hamsters alimentados com proteína de amaranto. Metodologia: Trinta hamsters foram divididos em 5 grupos e receberam dieta diferenciadas pela fonte protéica. Os grupos I e Icol receberam dieta com 20% de proteína de amaranto e os grupos caseína C e Ccol receberam dieta com 20% de caseína. Os grupos \"col\" apresentavam dieta com 0,1% de colesterol e 13,5% de gordura de coco. O metabolismo lipídico foi acompanhado através do monitoramento das concentrações plasmáticas de colesterol total, triacilgliceróis, HDL, e fração não-HDL nos animais. A excreção de colesterol e ácidos biliares foram quantificados nas fezes dos animais e o grau de esteatose hepática foi determinada através de análises histológicas do lobo direito do fígado. A atividade da enzima HMGR nos fígados foi medida por meio do Kit CS 1090 da Sigma-Aldrich com adaptações segundo Cong et al, 2012. A análise é baseada em espectrometria com absorbância de 340nm a 37ºC, que representa a oxidação de NADPH pela HMG-CoA redutase, na presença do substrato HMG-CoA. Conclusões: A proteína de amaranto pode ser considerado um aliado na redução dos agravos gerados pela dislipidemia, uma vez que reduziu significativamente os níveis de colesterol plasmático e gordura hepática, além de ser demonstrado seu efeito na redução da atividade da enzima HMG-CoA redutase dos animais hipercolesterolemizados que se alimentaram com proteína de amaranto. Uma vez verificado o efeito hipocolesterolemizante e seu possível mecanismo de ação por meio da enzima HMG-CoA redutase, espera-se com isso, estimular o consumo pela população brasileira produção de amaranto no Brasil, como alternativa para diversificar a dieta e a agricultura. / Introduction: Nowadays, Non-Communicable Chronic Diseases (NCCD) are a major challenge in health public. It is evident the role of diet in the control of cholesterol and incidence of cardiovascular disease. In this sense, amaranth arouses great interest due to its hypocholesterolemic property. Studies suggest that amaranth\'s hypocholesterolemic effect is associated with the inhibition of the enzyme HMG-CoA reductase, known as the key process to the endogenous cholesterol synthesis. Objective: Evaluate the hepatic enzymatic activity of HMG-CoA reductase in hamsters fed with amaranth protein. Methodology: Amaranth protein was isolated according to the conventional isoelectric precipitation methodology. Thirty hamsters were divided in 5 groups and were fed diets with different protein source. Experimental groups (I and lcol) had a diet containing 20% of protein amaranth and control groups(C and Cool) received a diet with 20% of casein. Moreover, groups \"col\" had also a diet with 0.1% cholesterol and 13.5% coconut oil in their composition. The lipid metabolism was accompanied through monitoring of plasma concentrations of total cholesterol, triglycerides, HDL and non-HDL fraction in animals. Excretion of cholesterol and bile acids were quantified in the feces of animals and the degree of hepatic steatosis was determined by histological analysis of the liver\'s right lobe. The HMGR enzyme activity in the liver was measured by the CS 1090 Kit from Sigma-Aldrich adjusted in accordance with Cong et al, 2012. The analysis is based on spectrometry with absorbance of 340nm at 37 ° C, which represents the oxidation of NADPH by HMG-CoA reductase in the presence of HMG-CoA substrate. Conclusions: Amaranth protein can be considered as an ally in reducing of injuries generated by dyslipidemia, since it significantly reduced levels of plasma cholesterol and hepatic fat. Furthermore, it was demonstrated its effect on reducing activity of HMG-CoA reductase enzyme in hypercholesterolemic animals, which were fed with amaranth protein. Therefore, once verified the hypocholesterolemic effect of amaranth and its possible action mechanism through HMG-CoA reductase enzyme, stimuli on the production of amaranth are expected as an alternative to diversify the diet and agriculture.