RESUMO
BACKGROUND: Obesity has been linked to gastrointestinal disorders, and the loss of myenteric neurons in the intestine caused by high-fat diets (HFD) has been attributed to changes in microbiota and lipotoxicity. We investigated whether the prebiotic inulin modulates bacterial populations and alleviates neuronal loss in mice fed HFD. METHODS: Swiss mice were fed purified rodent diet or HFD (59% kcal fat), or both diets supplemented with inulin for 17 weeks. Intestinal motility was assessed and a metagenome analysis of the colonic microbiota was performed. The gene expression of inflammatory markers was evaluated, and immunofluorescence was performed for different types of myenteric neurons and glial cells in the distal colon. KEY RESULTS: The HFD caused obesity and delayed colonic motility. The loss of myenteric neurons and glial cells in obese mice affected all of the studied neuronal populations, including neurons positive for myosin-V, neuronal nitric oxide synthase, vasoactive intestinal peptide, and calretinin. Although obese mice supplemented with inulin exhibited improvements in colonic motility, neuronal, and glial cell loss persisted. The HFD did not altered the expression levels of inflammatory cytokines in the intestine or the prevalence of the major groups in microbiota, but inulin increased the proportion of the genus Akkermansia in the obese mice. CONCLUSIONS AND INFERENCES: In Swiss mice, the HFD-induced neuronal loss but did not change the major groups in microbiota. This suggests that, despite the increase in the beneficial bacteria, other factors that are directly linked to excess dietary lipid intake affect the enteric nervous system.
Assuntos
Dieta Hiperlipídica/efeitos adversos , Microbioma Gastrointestinal , Plexo Mientérico/patologia , Neurônios/patologia , Obesidade/patologia , Animais , Motilidade Gastrointestinal/fisiologia , Inulina/farmacologia , Masculino , Camundongos , Obesidade/etiologia , Probióticos/farmacologiaRESUMO
Benign prostatic hyperplasia (BPH) is the most common cause of lower urinary tract symptoms (LUTS) in older men. In this regard, recent studies have attempted to define the relationships between prostatic fibrosis, LUTS, and increased expression of transforming growth factor ß1 (TGF ß1) in BHP. Therapeutic approaches for BPH such as 5-α-reductase inhibitors and alpha-adrenergic blocking agents increase TGF ß1 expression in the prostatic tissue. Here, we investigated the effects of the 5-α-reductase inhibitor-finasteride-on rat ventral prostate tissue, especially with regard to the tissue distribution and gene expression of fibrillar collagens. Adult Wistar rats (n = 15) were treated with finasteride (25 mg/kg/day) by subcutaneous injection for 7 and 30 days. Age-matched, vehicle-treated (n = 15) adult Wistar rats were used as control. Finasteride treatment reduced prostate size and increased the area of types I and III collagen fibers in the prostatic stroma. As expected, TGF ß1 mRNA expression was upregulated by finasteride treatment. However, COL1A1 and COL3A1 mRNA expressions decreased after both 7 and 30 days of finasteride treatment, suggesting that finasteride treatment promotes prostate parenchyma and stroma changes, which lead to the observed types I and III collagen remodeling without de novo collagen synthesis. The upregulation of TGF ß1 mRNA and protein associated with the 5-α-reductase inhibitor is more closely related to epithelial and stromal cell death pathways than to prostatic fibrosis.
Assuntos
Colágenos Fibrilares/genética , Finasterida/farmacologia , Próstata/efeitos dos fármacos , Fator de Crescimento Transformador beta1/biossíntese , Animais , Colágenos Fibrilares/biossíntese , Expressão Gênica/efeitos dos fármacos , Masculino , Próstata/metabolismo , Próstata/fisiologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos , Ratos Wistar , Ativação Transcricional/efeitos dos fármacos , Fator de Crescimento Transformador beta1/genética , Regulação para Cima/efeitos dos fármacosRESUMO
NEW FINDINGS: What is the central question of this study? We investigated the effects of physical training on phenotypic (fibre-type content) and myogenic features (MyoD and myogenin expression) in skeletal muscle during the transition from cardiac hypertrophy to heart failure. What is the main finding and its importance? We provide new insight into skeletal muscle adaptations by showing that physical training increases the type I fibre content during the transition from cardiac hypertrophy to heart failure, without altering MyoD and myogenin expression. These results have important clinical implications for patients with heart failure, because this population has reduced muscle oxidative capacity. The purpose of this study was to investigate the effects of physical training (PT) on phenotypic features (fibre-type content) and myogenic regulatory factors (MyoD and myogenin) in rat skeletal muscle during the transition from cardiac hypertrophy to heart failure. We used the model of ascending aortic stenosis (AS) to induce heart failure in male Wistar rats. Sham-operated animals were used as age-matched controls. At 18 weeks after surgery, rats with ventricular dysfunction were randomized into the following four groups: sham-operated, untrained (Sham-U; n = 8); sham-operated, trained (Sham-T; n = 6); aortic stenosis, untrained (AS-U; n = 6); and aortic stenosis, trained (AS-T; n = 8). The AS-T and Sham-T groups were submitted to a 10 week aerobic PT programme, while the AS-U and Sham-U groups remained untrained for the same period of time. After the PT programme, the animals were killed and the soleus muscles collected for phenotypic and molecular analyses. Physical training promoted type IIa-to-I fibre conversion in the trained groups (Sham-T and AS-T) compared with the untrained groups (Sham-U and AS-U). No significant (P > 0.05) differences were found in type I or IIa fibre content in the AS-U group compared with the Sham-U group. Additionally, there were no significant (P > 0.05) differences in the myogenic regulatory factors MyoD and myogenin (gene and protein) expression between the groups. Therefore, our results indicate that PT may be a suitable strategy to improve the oxidative phenotype in skeletal muscle during the transition from cardiac hypertrophy to heart failure, without altering MyoD and myogenin.
Assuntos
Cardiomegalia/metabolismo , Cardiomegalia/patologia , Insuficiência Cardíaca/metabolismo , Insuficiência Cardíaca/patologia , Proteína MyoD/metabolismo , Miogenina/metabolismo , Condicionamento Físico Animal/fisiologia , Animais , Masculino , Músculo Esquelético/metabolismo , Músculo Esquelético/patologia , Oxirredução , Ratos , Ratos WistarRESUMO
Skeletal muscle growth is regulated by differential expression of myogenic regulatory factors (MRFs). We evaluated hyperplasia, hypertrophy and quantitative expression of MRFs MyoD and myogenin in 45, 90, 180, and 400 days post-hatching (dph) and adult pacu (Piaractus mesopotamicus) skeletal muscle. Transverse sections of white dorsal muscles were obtained to evaluate hypertrophy and hyperplasia. MyoD and myogenin gene expression was determined by reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR). Pacu skeletal muscle had similar morphology at all stages. The highest and the lowest frequencies of fiber diameters <20 µm were found at the 45 dph and adult stages, respectively. Their frequency was similar in the 90, 180, and 400 dph stages. The highest percentage of >50 µm diameter fibers were found in 180 and 400 dph, and adult fish. Hyperplasia was the main mechanism observed in pacu skeletal muscle growth at 45dph; this declined through 90, 180, and 400 dph and remained low in adult fish; the latter presented hypertrophy as the main mechanism responsible for skeletal muscle growth. The high frequencies of 20-50 µm diameter fibers at 90, 180, and 400 dph can be related to intense hypertrophy. The mRNA levels for MyoD and myogenin were similar in 45, 90, and 400 dph and adult fish, peaking at 180 dph. The high MyoD expression at 180 dph can be related to intense myoblast proliferation and hyperplasia, while high myogenin expression can be related to intense myoblast differentiation and fusion during hypertrophy. MyoD and myogenin expression patterns in adults can respectively be associated with myoblast proliferation and differentiation, which both contribute to hypertrophy. Differential MyoD and myogenin expression in pacu white muscle probably is associated with differences in growth patterns during the stages analyzed. In this study, the 180 dph pacu could represent an interesting phase to investigate suitable strategies in commercial fish production focusing on skeletal muscle growth improvement to raise healthy, fast-growing fish.
Assuntos
Peixes/fisiologia , Regulação da Expressão Gênica , Músculo Esquelético/fisiologia , Proteína MyoD/biossíntese , Miogenina/biossíntese , Animais , Peixes/genética , Peixes/crescimento & desenvolvimento , Perfilação da Expressão Gênica , Hipertrofia , Músculo Esquelético/crescimento & desenvolvimento , Proteína MyoD/genética , Miogenina/genética , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
Skeletal muscle is the edible part of the fish. It grows by hypertrophy and hyperplasia, events regulated by differential expression of myogenic regulatory factors (MRFs). The study of muscle growth mechanisms in fish is very important in fish farming development. Pacu (Piaractus mesopotamicus) is one of the most important food species farmed in Brazil and has been extensively used in Brazilian aquaculture programs. The aim of this study was to analyze hyperplasia and hypertrophy and the MRF MyoD expression pattern in skeletal muscle of pacu (P. mesopotamicus) during juvenile and adult growth stages. Juvenile (n=5) and adult (n=5) fish were anaesthetized, sacrificed, and weight (g) and total length (cm) determined. White dorsal region muscle samples were collected and immersed in liquid nitrogen. Transverse sections (10 microm thick) were stained with Haematoxilin-Eosin (HE) for morphological and morphometric analysis. Smallest fiber diameter from 100 muscle fibers per animal was calculated in each growth phase. These fibers were grouped into three classes (<20, 20-50, and >50 microm) to evaluate hypertrophy and hyperplasia in white skeletal muscle. MyoD gene expression was determined by semi-quantitative RT-PCR. PCR products were cloned and sequenced. Juvenile and adult pacu skeletal muscle had similar morphology. The large number of <20 microm diameter muscle fibers observed in juvenile fish confirms active hyperplasia. In adult fish, most fibers were over 50 microm diameter and denote more intense muscle fiber hypertrophy. The MyoD mRNA level in juveniles was higher than in adults. A consensus partial sequence for MyoD gene (338 base pairs) was obtained. The Pacu MyoD nucleotide sequence displayed high similarity among several vertebrates, including teleosts. The differential MyoD gene expression observed in pacu white muscle is possibly related to differences in growth patterns during the phases analyzed, with hyperplasia predominant in juveniles and hypertrophy in adult fish. These results should provide a foundation for understanding the molecular control of skeletal muscle growth in economically important Brazilian species, with a view to improving production quality.