Rat Intestinal Acetic Acid and Butyric acid and Effects of Age, Sex, and High-fat Diet on the Intestinal Levels in Rats

BACKGROUND: High-fat diet is known to be implicated in the pathogenesis of various metabolic disorders related to an inflammatory response. The aim of this study was to investigate the influence of high-fat diet for intestinal acetic acid and butyric acid concentrations which are related to inflammation-associated colon cancer risk. METHODS: Both male and female rats of 6, 31, 74 and 104-week of age were fed chow diet or high-fat diet for 8 weeks. Body weight and food intake were measured weekly during the feeding period. Intestinal acetic acid and butyric acid levels were measured by high-performance liquid chromatography from luminal contents of ileum and cecum. RESULTS: Male rats showed greater weight change than female rats in every age. Calorie-adjusted food intake was also higher in male rats compared to female rats. Male rats showed similar intake of food in every age while 31-week old female rats showed increased intake, which was decreased at 74-week and 104-week of age. The ileal acetic acid concentration was increased in male rats fed high-fat diet, while female rats fed high-fat diet showed no significant change in the ileal acetic acid level. On the other hand, butyric acid almost disappeared in high-fat diet fed rats regardless of sex. CONCLUSIONS: High-fat diet increases the intestinal acetic acid concentration while reducing the butyric acid concentration which may account for increased risk of inflammation-associated colon cancer.

Remodelamento do fígado, pâncreas e tecido adiposo em modelo experimental de 'síndrome metabólica' tratado com telmisartana, sitagliptina e metformina / Remodeling of the liver, pancreas and adipose tissue in an experimental model of metabolic syndrome treated with telmisartan, sitagliptin and metformin

A intervenção farmacológica pode minimizar ou até mesmo reverter o remodelamento adverso em órgãos num modelo de síndrome metabólica. Este trabalho teve como objetivo avaliar os efeitos das monoterapias e associações medicamentosas sobre a morfologia do tecido adiposo, remodelamento hepático e pancreático em camundongos C57b1/6 alimentados com dieta very high-fat. Camundongos C57b1/6 machos foram alimentados com dieta very high-fat (HF, 60% de lipídios) ou dieta padrão (SC, 10% de lipídios) por 10 semanas, quando foram iniciados os tratamentos: HF-T (HF + Telmisartana, 5.2mg/Kg/dia), HF-S (HF + Sitagliptina, 1.08g/Kg/dia), HF-M (HF + Metformina, 310.0mg/Kg/dia) e as associações medicamentosas HF-TM, HF-TS e HF-SM. Os grupos tratados também tiveram livre acesso à dieta high fat e os tratamentos duraram 6 semanas. Técnicas morfométricas, estereológicas, imunohistoquímicas, ELISA, western blotting e microscopia eletrônica foram utilizadas. A dieta high-fat causou sobrepeso, intolerância oral à glucose, hiperinsulinemia, hipertrofia de ilhotas e adipócitos, grau 2 de esteatose hepatica (<33%) redução da expressão de PPAR-alfa e de GLUT-2, concomitante com aumento da expressão de SREBP-1 no grupo HF (P<0.0001). Por outro lado, todos os tratamentos resultaram resultaram em perda de peso significativa, reversão da resistência à insulina, hipertrofia de ilhotas e adipócitos e alívio da esteatose hepática. Somente os grupos HF-T e HF-TS apresentaram massa corporal similar ao grupo SC ao final do experimento, sendo que o último também apresentou reversão da esteatose hepática. O aumento da expressão do PPAR-alfa paralelamente ao decréscimo da expressão do SREBP-1 explica os achados favoráveis para o fígado. A normalização do tamanho do adipócito foi consistente com os níveis maiores de adiponectina e com a redução dos níveis de TNT-alfa (P<0.0001) nos grupos tratados. Todos os tratamentos foram eficazes para controlar a síndrome metabólica. Os melhores resultados ...

Pharmacological intervention can minimize or even reverse remodeling due to metabolic syndrome. This work sought to evaluate the effects of monotherapies and combinations of drugs on insulin sensitivity, adipose tissue morphology, pancreatic and hepatic remodeling in C57BL/6 mice fed a high-fat diet. Male C57BL/6 mice were fed a very high-fat diet (HF, 60% lipids) or standard chow (SC, 10% lipids) over 10 weeks, after which drug treatments began: HF-T (HF + Telmisartan, 5.2mg/Kg/day), HF-S (HF + Sitagliptin, 1.08g/Kg/day), HF-M (HF + Metformin, 310.0mg/Kg/day) and the drug combinations HF-TM, HF-TS and HF-SM. Treated groups also had free access to HF diet and treatments lasted 6 weeks. Morphometry, stereological tools, immunostaining, ELISA, Western blotting and electron microscopy were used. The HF diet yielded an overweight phenotype, oral glucose intolerance, hyperinsulinemia, hypertrophied islets and adipocytes, stage 2 steatosis (<33%) and reduced liver PPAR-alpha and GLUT-2, concomitant with enhanced SREBP-1 expression, in the HF group (P<0.0001). Conversely, all drug treatments resulted in significant weight loss, reversed insulin resistance, islet and adipocyte hypertrophy and alleviated hepatic steatosis. Only HF-T and HF-TS presented body weights similar to SC mice at the end of the experiment and the latter treatment reversed hepatic steatosis. Increased PPAR-alpha immunostaining parallel to higher GLUT-2 and reduced SREBP-1 expression explain the favourable hepatic outcomes. Restoration of adipocyte size was consistent with higher adiponectin levels and lower TNF-alpha levels (P<0.0001) in treated groups. In conclusion, all treatments were effective in controlling metabolic syndrome. The best results were achieved using telmisartan and sitagliptin as monotherapies or as a dual treatment, combining partial PPAR-gamma agonism and PPAR-alpha activation in the liver with extended incretin action

Metabolism and secretory function of white adipose tissue: effect of dietary fat

Approximately 40 percent of the total energy consumed by western populations is represented by lipids, most of them being ingested as triacylglycerols and phospholipids. The focus of this review is to analyze the effect of the type of dietary fat on white adipose tissue metabolism and secretory function, particularly on haptoglobin, TNF-α, plasminogen activator inhibitor-1 and adiponectin secretion. Previous studies have demonstrated that the duration of the exposure to the high-fat feeding, amount of fatty acid present in the diet and the type of fatty acid may or may not have a significant effect on adipose tissue metabolism. However, the long-term or short-term high fat diets, especially rich in saturated fatty acids, probably by activation of toll-like receptors, stimulated the expression of proinflammatory adipokines and inhibited adiponectin expression. Further studies are needed to investigate the cellular mechanisms by which dietary fatty acids affect white adipose tissue metabolism and secretory functions.

Aproximadamente 40 por cento do total de energia consumida pela população ocidental é representada pelos lipídios, a maioria dela sendo ingerida na forma de triglicerídeos e fosfolipídios. O foco desta revisão foi analisar o efeito dos tipos de gordura da dieta sobre o metabolismo e função secretora do tecido adiposo branco, principalmente, sobre a secreção de haptoglobina, TNF-α, inibidor do ativador de plasminogênio-1 e adiponectina. Estudos prévios demonstraram que durante a exposição de dietas hiperlipídicas, a quantidade e o tipo de ácidos graxos presentes na dieta podem ou não ter um efeito significante sobre o metabolismo do tecido adiposo. Entretanto, o tratamento a curto ou longo prazo com dieta hiperlipídica, especialmente rica em ácidos graxos saturados, provavelmente por ativar receptores toll-like, estimula a expressão de adipocinas pró-inflamatórias e inibe a expressão de adiponectina. Estudos adicionais são necessários para investigar os mecanismos celulares pelos quais os ácidos graxos da dieta afetam a função secretória e metabólica do tecido adiposo branco.