HMGA1 is a novel downstream nuclear target of the insulin receptor signaling pathway

High-mobility group AT-hook 1 (HMGA1) protein is an important nuclear factor that activates gene transcription by binding to AT-rich sequences in the promoter region of DNA. We previously demonstrated that HMGA1 is a key regulator of the insulin receptor (INSR) gene and individuals with defects in HMGA1 have decreased INSR expression and increased susceptibility to type 2 diabetes mellitus. In addition, there is evidence that intracellular regulatory molecules that are employed by the INSR signaling system are involved in post-translational modifications of HMGA1, including protein phosphorylation. It is known that phosphorylation of HMGA1 reduces DNA-binding affinity and transcriptional activation. In the present study, we investigated whether activation of the INSR by insulin affected HMGA1 protein phosphorylation and its regulation of gene transcription. Collectively, our findings indicate that HMGA1 is a novel downstream target of the INSR signaling pathway, thus representing a new critical nuclear mediator of insulin action and function

Nothing in excess - lessons learned from the expression of high-mobility group proteins type A in non-cancer and cancer cells

High-mobility group A (HMGA) proteins are major transcription regulators which are abundantly and ubiquitously expressed in undifferentiated cells but present at a low level in somatic cells of adult organisms. Up-regulation of HMGA expression is a frequent finding in cancer, either via direct stimulation of expression by constitutively expressed proto-oncogenic factors such as MYC and JUN or by rearrangements rendering the expression of the HMGA proteins not suppressible by inhibitory factors such as miRNAs. Rearrangements of the HMGA genomic loci resulting in disabling of the control mechanisms of their expression are often seen in tumours of various origin. A direct relationship between the level of expression of HMGA in mitochondria and the level of accumulation of oxidative damage in cancer cells has been recently noted. On the other hand, mammalian cells deficient in HMGA1 expression are also deficient in utilization of glucose and show the impairment in expression of the insulin receptor and the high levels of oxidative damage of DNA characteristic of diabetes type 2 and the related condition metabolic syndrome. Insulin resistance and metabolic syndrome could be viewed as a premalignant state in which DNA damage is slowly accumulating until the repair machinery of the cell cannot withstand the constant oxidative barrage and surrenders to neoplastic transformation

Cyclin-dependent kinases as drug targets for cell growth and proliferation disorders. A role for systems biology approach in drug development. Part II - CDKs as drug targets in hypertrophic cell growth. Modelling of drugs targeting CDKs

Cyclin-dependent kinases (CDKs) are key regulators of cell growth and proliferation. Impaired regulation of their activity leads to various diseases such as cancer and heart hypertrophy. Consequently, a number of CDKs are considered as targets for drug discovery. We review the development of inhibitors of CDK2 as anti-cancer drugs in the first part of the paper and in the second part, respectively, the development of inhibitors of CDK9 as potential therapeutics for heart hypertrophy. We argue that the above diseases are systems biology, or network diseases. In order to fully understand the complexity of the cell growth and proliferation disorders, in addition to experimental sciences, a systems biology approach, involving mathematical and computational modelling ought to be employed

Differential genetic advantages in youth and in aging, or how to die healthy

Human society ages at a steady rate, that is, the proportion of adult and elderly individuals increases constantly because of improved living conditions and the advances in medical care. This means that very soon the tradeoff between the advantages in old age conferred by alleles disadvantageous or neutral in young age would begin to show, providing the fascinating opportunity of studying the interplay between genetic factors and environment outside the framework of reproductive capacity and in the unique milieu of the aging cell. Being healthy and/or health-conscious in youth does not guarantee for successful aging or even that the person would live up to the average life expectancy of the population. Therefore, successful aging and longevity are related to a healthy-conscious attitude to a degree only. The present paper reviews the basic genetic and evolutionary mechanisms which have operated during human history so as to ensure survival of humankind and the possible factors preventing or contributing to successful aging

Estimating the impact of diabetes on employment in Taiwan

This paper investigates the impact of diabetes on employment based on the 2005 National Health Interview Survey in Taiwan using a recursive bivariate probit model. The findings show that diabetes has a negative and significant effect on employment, and that the magnitude is larger for men than for women. The results of this study also suggest that neglecting the potential endogeneity of diabetes will lead to an underestimation of the negative impact of diabetes on employment.diabetes, employment, Taiwan

NUCKS Is a Positive Transcriptional Regulator of Insulin Signaling.

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Diabetes Mellitus: Metabolic Effects and Oxidative Stress

Diabetes mellitus is a complex polygenic pathology, which is characterized by numerous metabolic disorders. Progressive hyperglycemia developing during this disease causes clinically significant tissue damage and is considered as a main risk factor of micro- and macrovascular complications leading to retinopathy, nephropathy, and neuropathy. Hyperglycemia depended oxidative stress and impairments in nitric oxide bioavailability play an essential role in the pathogenesis of diabetes and its complications. Homeostasis of glucose maintained by metabolic effects of insulin includes an increase of glucose uptake by skeletal muscles and suppression of glucose production by the liver. M. Brownlee (2005) put forward a hypothesis assuming that oxidative stress is the main mechanism of diabetic tissue damages. According to this hypothesis, mitochondrial dysfunction and superoxide anion radical hyperproduction by mitochondria is the principal mechanism of activation of four pathways of hyperglycemia-induced impairments under diabetes. Two cell signaling cascades regulate the glucose homeostasis: insulin-mediated glucose uptake (IMGU) in skeletal muscles, liver, and heart and glucose-stimulated insulin secretion (GSIS) in pancreatic β-cells. In addition to nonspecific irreversible oxidative damage of DNA, protein and lipid molecules reactive oxygen and nitrogen species induce cell and tissue damage, activating a number of cell stress-sensitive signaling cascades. Stress-dependent serine phosphorylation of insulin receptor substrate (IRS) proteins decreases its capacity for tyrosine phosphorylation and may accelerate degradation of IRS. This process underlies the molecular mechanism of oxidative stress-induced insulin resistance

Polymorphic micro-RNA targets and risk of colorectal cancer

Recent evidence indicate that small non-coding RNA molecules, called micro-RNAs (miRNA), can bind to the 3’UTRs of mRNAs and interfere with their translation, thereby regulating cell growth, differentiation, apoptosis, and tumorigenesis. Genetic polymorphisms can reside on miRNA binding sites. Thus, it is conceivable that the miRNA regulation may be affected by polymorphisms on the 3’ UTRs. Since gene de-regulation is one of the key mechanisms by which cells can progress to cancer, we hypothesize that common polymorphisms within miRNA target binding sites could play a role in the individual risk of cancer. In the present study, we selected the 3’UTR regions of 129 genes candidate for colorectal cancer (CRC) and we identified putative miRNA binding sites by specialized algorithms (PicTar, DianaMicroT, miRBase, miRanda, TargetScan, and microInspector). We evaluated the SNPs for their ability to affect the binding of the miRNA with its target, by assessing the variation of Gibbs free energy between the two alleles of each SNP. We found 15 common polymorphisms. We added to this list 8 SNPs in miRNA sequences. All the polymorphisms were further investigated by a case-control association studies. The study was carried out on a series of cases and controls from Czech Republic, a population with the highest worldwide incidence of CRC. We found statistically significant associations between risk of CRC and variant alleles of CD86 (OR=2.74 95%CI=1.24-6.04, for the variant homozygotes) and INSR genes (OR=1.94; 95%CI=1.03-3.66, for the variant homozygotes). Then, these two polymorphisms were genotyped in three different populations: Spanish, Italian, and German.The statistical analyses for all the samples (Czech, Spanish, Italian, and German) confirmed the assciation between risk of CRC and the polymorphisms in CD86 and INSR. These results are the first reporting positive association between miRNA-binding SNPs sequences and cancer risk

Role of inflammation in the pathogenesis of insulin resistance in obesity : specific role of reactive oxygen and reactive nitrogen species

L’inflammation chronique associée à l’obésité contribue à la pathogénèse de plusieurs troubles métaboliques dont la résistance à l’insuline. Cette inflammation est associée avec le développement du stress oxydant et est reconnue comme un facteur impliqué dans l’inhibition de la signalisation de l’insuline. Ainsi, le but de ces études était d’évaluer le rôle du stress oxydant dans le développement de la résistance à l’insuline associée à l’inflammation. En particulier, nous avons cherché à évaluer le rôle de l’ion superoxyde et de radicaux lipidiques qui, associés à l’induction de la forme inductible de la NO synthase (iNOS), pourraient jouer un rôle clé dans la promotion de nitration de tyrosine des protéines impliquées dans la signalisation d’insuline, ainsi que dans la promotion des troubles métaboliques associés à l’obésité. Dans la première étude, nous avons démontré que le traitement d’adipocytes avec des cytokines induit l’expression de l'isoforme NADPH oxidase 3 (NOX3) de la famille des NADPH oxydases (NOX) et parallèlement augmente la production de l'ion superoxyde. Ce traitement a aussi augmenté la lipolyse et la phosphorylation de la lipase hormono-sensible. Fait intéressant, l’inhibition de l’activité de NOX avec le Diphenyleneiodonium (DPI), a renversé l’effet des cytokines sur la lipolyse, la production de superoxyde et la phosphorylation de la lipase hormono-sensible. De plus, l’inhibition spécifique de l’expression de NOX3 via l'expression d'un siRNA a eu le même effet que le DPI. Cela indique que NOX3 est la source majeure de production de superoxyde induit par l’inflammation et ainsi régule négativement la lipolyse par l’augmentation de l’activité de la lipase hormono-sensible. Dans la deuxième étude, nous avons identifié un rôle pour NOX3 et l'anion superoxyde dans le mécanisme de nitration de tyrosines sur Akt dans les cellules hépatiques FAO. Aussi, l’expression de NOX3 a augmenté dans les cellules hépatiques primaires traitées avec cytokines en même temps que l’augmentation de 3-nitrotyrosine, une empreinte reconnue de la formation de nitrotyrosine. Nous avons observé qu’une diète riche en lipides a pour effet d’augmenter la nitration sur tyrosine dans les foies de souris ainsi que dans les cellules hépatiques primaires isolées des foies de ces souris. De plus, cette diète a augmenté la nitration de tyrosines sur Akt dans le foie de souris obèses. Finalement, nous avons identifié deux résidus, tyrosine 152 et tyrosine 38, qui sont nitratés sur Akt1, et qui pourraient réguler négativement l’activité d’Akt lorsque nitratés. Dans la troisième étude, nous avons démontré que le captage des radicaux lipides avec le "spin trap" α -(4-Pyridyl-1-oxide)-N-tert-butylnitrone (POBN) dans les souris nourries avec une diète riche en lipides a diminué la masse adipeuse comparativement avec les souris obèse non traitées. Cet effet a été associé à une amélioration de la tolérance au glucose et de la sensibilité à l’insuline, ainsi que d'une diminution de l’inflammation dans la tissu adipeux. En plus, on a remarqué une amélioration de la fonction mitochondriale dans le muscle et le tissu adipeux. Dans le foie, la traitement avec POBN a empêché l’accumulation des lipides et a amélioré le métabolisme de glucose. L'ensemble de nos études démontre le rôle de l'anion superoxyde généré par NOX3 dans le mécanisme de nitration de tyrosine dans le foie et la modification de la fonction métabolique dans les adipocytes. Aussi, nous avons identifié deux tyrosines nitratées sur Akt1 qui pourraient être impliquées dans la régulation de son activité. Enfin, nous avons montré que POBN semble d’avoir un effet préventif sur l’obésité qui est associé avec l’amélioration des plusieurs paramètres métaboliques.Chronic low-grade inflammation is considered one of the triggers of obesity-associated insulin resistance. Metabolic inflammation goes along with increased oxidative and nitrosative stress, but whether this promotes insulin resistance in obesity remains ill-defined. Thus, the primary objective of this thesis was to study the role of oxidative and nitrosative stress in the development of inflammation mediated insulin resistance and in particular to highlight the role of superoxide anion production, lipid radical generation, and iNOS induction, in mediating tyrosine nitration of insulin signaling proteins and other metabolic dysfunctions associated with obesity. In chapter I, we showed for the first time that treatment of adipocytes with cytokines induced NADPH oxidase-3 (NOX3) expression along with increasing superoxide production. Cytokine treatment also increased lipolysis as indicated by measuring free glycerol release and caused increase in the phosphorylation of hormone sensitive lipase. Interestingly, pharmacological inhibition of NOX activity by Diphenyleneiodonium (DPI) reversed the effect of cytokines on lipolysis and on the phosphorylation of HSL in line with decreasing superoxide production. Specific knockdown of NOX3 gene expression in adipocytes displayed the same effects as those exerted by DPI. These results indicate that NOX3 is the major NOX involved in superoxide production in 3T3L1 adipocytes and a regulator of lipolysis in inflammatory settings. In chapter II, we identified a new role of NOX3 and superoxide production in mediating tyrosine nitration on Akt in FAO hepatic cells. NOX3 expression was increased in primary hepatocytes after cytokine treatment together with an increase in 3-nitrotyrosine. Interestingly, primary hepatocytes isolated from high fat (HF) fed mice displayed more tyrosine nitration when compared to primary hepatocytes isolated from mice on chow diet. Also, we showed for the first time a tendency for high fat feeding to increase tyrosine nitration specifically on Akt. More importantly, two novel tyrosine nitrated sites on Akt1 were identified: tyrosine 152 and tyrosine 38, which seem to play a role in negatively regulating Akt activity when tyrosine nitrated. In chapter III, scavenging lipid radicals by α -(4-Pyridyl-1-oxide)-N-tert-butylnitrone (POBN) reversed the metabolic disorders caused by HF feeding in mice. POBN treated mice exhibited decrease in fat mass when compared to their HF counterparts. This effect was associated with enhanced glucose tolerance and insulin sensitivity. Also, adipose tissue inflammation was alleviated and mitochondrial function was ameliorated, insulin signaling in skeletal muscle was restored and mitochondrial oxidative metabolism was also enhanced. In the liver, POBN treatment prevented fat accumulation and enhanced lipid and glucose metabolism. Together these results highlight the important role of NOX3 generated superoxide in mediating tyrosine nitration in liver and in altering metabolic dysfunction in adipocytes. Also, two important tyrosine nitrated sites on Akt were identified that may possibly be involved in regulating its activity. Finally, the lipid radical scavenger, POBN, displayed anti-obesity effects in HF fed mice and this effect was associated with amelioration of several metabolic parameters

Modulation of ruminal biohydrogenation in sheep through dietary tannins or energy sources

Tese de Doutoramento em Ciências Veterinárias na especialidade de Produção AnimalIn the present thesis, four experiments were conducted to study how ruminal biohydrogenation pathways can be modulated through dietary inclusion of tannin sources and to acquire a better comprehension about the occurence of t10-shifted biohydrogenation pathways. In the first experiment, in vitro batch incubations with 100 g/kg dry matter (DM) of extracts of chestnut tannins (mostly hydrolysable tannins) and quebracho, grape seed or rockrose (Cistus ladanifer) condensed tannins, as well as a control treatment were incubated for 6 h with ruminal fluid from fistulated sheep and a dehydrated lucerne-based substrate with 60 g/kg DM of sunflower oil. Grape seed and, to a lesser extent, C. ladanifer led to a higher disappearance of 18:2n-6 with a consequent higher production of c9,t11-18:2 and t11-18:1 than chestnut, quebracho and control. There was no clear innibition of 18:0 production with any of the extracts comparing with control. In the second experiment, rumen fistulated sheep were fed tannin extracts from mimosa condensed tannins, chestnut hydrolysable tannins or their mixture (100 g/kg DM) in a complete diet with sunflower and linseed oils (40 g/kg DM), following a change-over design (3 treatments, 4 sheep and 4 periods). There was a variable inhibition of ruminal biohydrogenation and a lower “trans-/cis-18:1” ratio in bacterial fractions with mimosa than with chestnut. Mimosa led to a lower fermentative activity, as well as a lower abundance of Fibrobacter succinogenes, Ruminococcus albus, Ruminococcus flavefaciens and Butyrivibrio proteoclasticus and higher abundance of Selenomonas ruminantium with a lower bacterial biomass estimate of dimethylacetals than chestnut. In the third experiment, two rumen fistulated rams were housed in metabolic cages and adapted to a wheat-based diet with 41 g/kg DM of sunflower oil. During the first two weeks of trial, the t10-shift occurred temporarily in both animals but in different moments. These results were probably due to individual variability of rumen microbiota, since, for a selected period of the trial, a lower bacterial diversity was found for ram 1 compared to ram 2. Moreover, the t10-shift was associated with an increase of total trans-18:1 and a decrease of 18:0. There was no clear association of t10-shift with rumen pH or its expression in blood plasma. In the fourth experiment, 40 lambs were fed, for 6 weeks, with complete diets containing barley or barley completely replaced for dehydrated citrus pulp, dehydrated beet pulp or soybean hulls. All diets were supplemented with an oil blend (soybean:fish oils, 59:10 g/kg DM). Overall, the t10-/t11-18:1 ratio was above 3 in meat and subcutaneous fat, although soybean hulls increased t11-18:1 and c9,t11-18:2 comparing with the other treatments. Citrus pulp led to the lowest gene expression of fatty acid synthase, while that of stearoyl-CoA desaturase was inferior for soybean hulls and beet pulp.RESUMO - Modulação da bioidrogenação ruminal em ovinos através de taninos ou de fontes energéticas da dieta - A dieta dos ruminantes é um dos principais determinantes que influencia a bioidrogenação (BH) ruminal. A inclusão de taninos na dieta, os quais são compostos fenólicos das plantas, pode aumentar a proporção, no rúmen e nos tecidos, de ácidos gordos (AG) bioactivos com efeitos benéficos na saúde humana, tais como os ácidos vacénico (t11-18:1) e ruménico (c9,t11-18:2; conjugado do ácido linoleico - CLA) derivados das vias t11 da BH. A maior quantidade de c9,t11-18:2 presente nos tecidos resulta da dessaturação de t11-18:1 pela estearoil-CoA dessaturase (SCD; Δ9-dessaturase). Contudo, na presença de dietas com alto teor em amido e baixo conteúdo em forragem, com ou sem suplementação com óleos ricos em ácidos gordos polinsaturados, pode ocorrer uma modificação das vias da BH com predomínio das vias t10 relativamente às t11 (o shift-t10) e o concomitante aumento de AG deletérios para a saúde, nomeadamente t10-18:1 e t10,c12-18:2. Na presente tese, foram realizadas duas experiências com o propósito de estudar o efeito da inclusão de diversos tipos de taninos como moduladores da BH (experiências 1 e 2) e duas experiências para obter uma melhor compreensão dos factores que determinam a ocorrência do shift-t10 (experiências 3 e 4). Em todos os estudos, foram incorporados óleos de origem vegetal ou animal nas dietas para aumentar a formação de intermediários da BH. Na primeira experiência, foi realizado um ensaio in vitro com 100 g/kg de matéria seca (MS) de extractos de taninos da castanha (maioritariamente taninos hidrolisáveis) e de extractos de taninos condensados de quebracho, de sementes de uva e de esteva (Cistus ladanifer), bem como um tratamento controlo (sem taninos). As incubações decorreram durante 6 h com fluido de rúmen de ovinos fistulados e um substrato à base de luzerna desidratada com 60 g/kg MS de óleo de girassol (2:1, rácio “foragem/concentrado”). A composição em AG dos tubos de incubação foi obtida por transesterificação combinada, seguida da separação dos ésteres metílicos dos AG por cromatografia gás-líquido e da sua identificação com espectrometria de massa. Determinaram-se também a produção de ácidos gordos voláteis (AGV) e o pH do rúmen, tendo-se verificado apenas pequenas diferenças no pH. Os tratamentos com extractos de uva e, menos marcadamente, de C. ladanifer causaram um maior desaparecimento de ácido linoleico (c9,c12-18:2; 18:2n-6) e um consequente aumento do total de trans-18:1, nomeadamente de t11-18:1, e de c9,t11-18:2, bem como uma diminuição do total de dimetilacetais (DMA), comparativamente aos extractos de castanha e de quebracho e ao controlo, embora, considerando o total de DMA, esta diferença não tenha sido significativa para o caso do quebracho. Não houve uma clara inibição da produção de ácido esteárico (18:0) com nenhum dos tratamentos em comparação com o controlo, apesar do extracto de uva ter originado uma menor proporção de 18:0 relativamente ao total de produtos da BH. Na segunda experiência, ovinos fistulados foram alimentados com extractos comerciais de taninos da mimosa (condensados), da castanha (hidrolisáveis) e de uma mistura de ambos (100 g/kg MS) incorporados numa dieta completa (1:1, rácio “foragem/concentrado”) suplementada com uma mistura de óleos de girassol e linho (40 g/kg MS), segundo um desenho experimental de “change-over” (3 tratamentos, 4 animais and 4 períodos). Os períodos experimentais tiveram a duração de 3 semanas, includindo 2 semanas de adaptação às dietas e 1 semana de recolha de amostras. As amostras de conteúdo do rúmen foram obtidas antes da refeição da manhã em 2 dias das últimas semanas de cada período com um intervalo de 2 dias entre recolhas. No primeiro dia de amostragem, recolheram-se os conteúdos totais do rúmen para obtenção das bactérias associadas às fracções sólida (SAB) e líquida (LAB), enquanto, no segundo dia, os conteúdos foram usados para avaliação da actividade fermentativa (análise de pH e AGV). Em ambos os dias de recolha, as amostras de conteúdo do rúmen foram utilizadas para a análise de AG, bem como para a extracção de DNA e posterior quantificação do número de cópias de 16S rRNA de bactérias seleccionadas do rúmen. No último dia, recolheram-se amostras de sangue antes e 3 h depois da refeição da manhã. As dietas com extracto de mimosa e com a mistura de extractos causaram uma inibição da BH ruminal em algumas réplicas dos tratamentos e a mimosa originou ainda um menor rácio “trans-/cis-18:1” nas fracções bacterianas, comparativamente à dieta com extracto de castanha. A dieta com mimosa levou ainda a uma menor concentração do total de AGV, bem como a uma inferior abundância de Fibrobacter succinogenes, Ruminococcus albus, Ruminococcus flavefaciens e Butyrivibrio proteoclasticus e a uma maior abundância de Selenomonas ruminantium, juntamente com um menor estimativa da biomassa bacteriana por DMA, em comparação com a castanha. Adicionalmente, o tratamento com mimosa originou um aumento do total de oxo-18:0, no plasma sanguíneo e no rúmen, em relação à castanha, enquanto, nas fracções bacterianas, este aumento verificou-se com a mistura de extractos comparativamente à média dos tratamentos com extractos de mimosa e de castanha. Na terceira experiência, dois carneiros fistulados foram colocados em caixas metabólicas e gradualmente adaptados a uma dieta à base de trigo com 41 g/kg MS de óleo de girassol. Durante os 29 dias de ensaio, recolheram-se amostras de conteúdo do rúmen, antes e 3h depois da refeição da manhã. Os conteúdos do rúmen foram também obtidos uma vez por semana a cada 1h30 entre as 9h30 e as 20h00 para a análise da composição em AG e dos grupos taxonómicos bacterianos, juntamente com amostras de sangue recolhidas antes e 3 h depois da refeição da manhã. O shift-t10 ocorreu progressiva e temporariamente nas primeiras duas semanas e coincidiu com um acréscimo de ingestão de alimento que se seguiu ao seu decréscimo. O padrão de indução do shift-t10 apresentou variabilidade individual, a qual foi provalmente causada por diferenças entre animais a respeito da microbiota do rúmen, na medida em que, num período definido do ensaio, verificou-se uma menor diversidade bacteriana no animal com maior rácio t10-/t11-18:1 (carneiro 1) do que no animal com menor rácio (carneiro 2). Considerando os grupos taxonómicos obtidos por pirossequenciação da região 16S rRNA do genoma bacteriano, a abundância dos filos Actinobacteria e, em menor extenção, Spirochaetae era maior no carneiro 1 em relação ao carneiro 2, contrariamente aos filos Bacteroidetes e Firmicutes. Para além disso, o shift-t10 estava associado ao aumento do total de trans-18:1 e à diminuição da produção de 18:0, bem como ao aumento prévio da formação de oxo-18:0 no rúmen. Não se verificou uma clara associação entre o estabelecimento do shift-t10 e a sua expressão no plasma sanguíneo e a redução do pH do conteúdo do rúmen. De facto, o aumento do rácio “t10-/t11-18:1” no rúmen não se encontrava relacionado com um maior rácio “t10-18:1/(t11-18:1 + c9,t11-18:2)” no plasma e, apenas num carneiro, ocorreu um aumento pós-prandial do rácio “t10-/t11-18:1” associado a uma redução do pH. Na quarta experiência, quarenta borregos foram alimentados, durante 6 semanas, com uma de quatro dietas completas (1:4, rácio “foragem/concentrado”) suplementadas com uma mistura de óleos de soja e de peixe (59:10 g/kg MS) e contendo, como principal fonte energética, cevada (42% MS) (cereal) ou cevada completamente substituída por polpa de citrinos desidratada, polpa de beterraba desidratada ou cascas de soja. Durante a experência, os parâmetros produtivos foram avaliados. Imediatamente após o abate dos animais, amostras de músculo Longissimus foram recolhidas para avaliação da expressão dos genes das enzimas síntase de ácidos gordos (FASN), SCD e acetil-CoA carboxilase (ACACA). Ao terceiro dia após o abate, obtiveram-se amostras de músculo e de gordura subcutânea para análise da composição em AG. A dieta com polpa de citrinos levou a uma redução do ganho de peso diário e a um aumento da probabilidade de desenvolver lesões mais severas de paraqueratose da mucosa do rúmen. As dietas com polpa de citrinos e com cascas de soja foram responsáveis pela diminuição da eficiência alimentar, comparativamente à dieta com cevada. Todos os tratamentos originaram um rácio “t10-/t11-18:1” acima de 3, na carne e na gordura subcutânea, apesar da dieta com cascas de soja ter causado um aumento de t11-18:1 e c9,t11-18:2 nos tecidos, comparativamente aos outros tratamentos. Adicionalmente verificou-se a menor expressão dos genes da FASN, com a dieta com polpa de citrinos, e da SCD, com as dietas com cascas de soja e polpa de beterraba.N/