RESUMEN
BACKGROUND: Obesity impairs homeostatic control of energy and is associated with chronic low-grade inflammation. Effects of glucagon-like peptide-1, the target in the gastrointestinal tract for anti-obesity drugs such as Liraglutide, were not properly associated with inflammation markers. This study investigated the effects of Liraglutide on metabolic and gastrointestinal parameters in a rat model of obesity. METHODS: Twenty-six Wistar rats with obesity were randomly distributed to receive saline (n = 10), 400 µg (n = 8), or 1200 µg of Liraglutide/kg/day (n = 8), subcutaneously for 30 consecutive days, once a day. Weight gain, feeding efficiency, caloric consumption, gastric motility, adiposity, histomorphometric, murinometric, biochemical parameters and cytokines TNF-α and TGF-ß1 in duodenal tissue were measured. Data were analysed by ANOVA, followed by Bonferroni post hoc or Kruskal-Wallis test, followed by Dunn's multiple comparison test. RESULTS: Liraglutide-treated animals had better feeding efficiency and higher caloric intake in a dose-dependent manner. Higher doses slowed gastric emptying and diminished the amplitude of gastric contractions. These effects were accompanied by decreases in intestinal muscle layer thickness and crypt depth. Liraglutide significantly reduced retroperitoneal and visceral white adipose tissue depots. High-dose treatment decreased levels of TNF-α and enhanced levels of TGF-ß1 in duodenal tissue. Liraglutide treatment provided significant reductions in total cholesterol, triglyceride and hepatic transaminases. CONCLUSIONS: Liraglutide reduced fat accumulation, improved metabolic parameters and downregulated levels of inflammatory signalling in duodenal tissue. Liraglutide at high doses controlled obesity-related outcomes, and such effects seemed to be driven by its action on glucagon-like peptide-1 receptors in the gastrointestinal tract slowing gastric motility.
Asunto(s)
Liraglutida , Factor de Crecimiento Transformador beta1 , Ratas , Animales , Liraglutida/farmacología , Liraglutida/uso terapéutico , Factor de Necrosis Tumoral alfa , Ratas Wistar , Péptido 1 Similar al Glucagón/farmacología , Péptido 1 Similar al Glucagón/uso terapéutico , Obesidad/tratamiento farmacológico , Obesidad/complicaciones , Inflamación/tratamiento farmacológico , Inflamación/complicaciones , Tracto Gastrointestinal , Hipoglucemiantes/uso terapéuticoRESUMEN
BACKGROUND: Obesity treatment includes less invasive procedures such as gastric plication (GP) surgery; however, its effects on gastrointestinal (GI) motility parameters are underestimated. We aimed to verify the metabolic and gastrointestinal effects of GP surgery in the rat obesity model. METHODS: A high-fat diet-induced obesity was used. Animals were allocated to four experimental groups: control sham (n = 6); control GP (n = 10); obese sham (n = 6); and obese GP (n = 10). Nutritional and murinometric parameters, gastric motility, glucose tolerance, histopathology, fat depots, leptin, and lipoproteins levels were evaluated 30 days after surgery. Data were analyzed by ANOVA followed by post Tukey or Kruskal-Wallis test followed by Dunn's multiple comparisons test. KEY RESULTS: Gastric plication decreased leptin levels, feed efficiency, and body weight gain. GP does not improve lipid profile in obese animals and however, ameliorates glucose tolerance in control and obese rats. GP did not improve the gastric emptying time or normalize the frequency of contractions disturbed by obesity. Surgery provides a remodeling process in the mucosa and muscularis mucosa layers, evidenced by leukocyte infiltration mainly in the mucosa layer. CONCLUSIONS & INFERENCES: Our study revealed the influence of the gastrointestinal tract on obesity is underestimated with pieces of evidence pointing out its important role as a target for surgical treatment.
Asunto(s)
Dieta Alta en Grasa , Leptina , Ratas , Animales , Obesidad/metabolismo , Estómago , GlucosaRESUMEN
Alternate-day fasting (ADF) is a nutritional intervention with modulatory and overall protective effects, but its role in the gastrointestinal (GI) tract is still uncertain. The aim of this study was to investigate the influence of ADF on the metabolic patterns and morphofunctional motility of the GI tract in rats. Thirty-two male Wistar rats were allocated into groups: control for 15 days (CON 15, n = 8), control for 30 days (CON 30, n = 8), ADF for 15 days (ADF 15, n = 8), and ADF for 30 days (ADF 30, n = 8). Blood glucose, body weight, and food and water consumption were measured. Frequency and amplitude of gastric contractions as well as gastric emptying time, small intestinal transit time, and cecum arrival time were measured. Intestinal histomorphometric, relative weight of organs, lipidogram, and leptin levels were also evaluated. ADF decreased water consumption and food consumption. The weight gain decreased; however, the relative kidney weight increased. ADF triggered an increase in the amplitude of gastric contractions and accelerated gastric emptying. However, small intestinal transit time was delayed in both ADF groups. Total cholesterol, triglycerides, non-HDL cholesterol, and very low-density lipoprotein cholesterol levels decreased, whereas villus height, depth of the crypts and thickness of the circular, and longitudinal muscular layers of intestine increased after ADF. In conclusion, our results showed ADF exert an effect on both metabolism and GI motility and impacts on overall digestive functions.
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Ayuno , Tracto Gastrointestinal , Ratas , Masculino , Animales , Ratas Wistar , Vaciamiento Gástrico , Colesterol , Tránsito GastrointestinalRESUMEN
Abstract Our aim was to evaluate the effects of cisplatin and dexamethasone alone and combined on gastric contractility and histomorphometry of BALB/c and C57BL/6 mice. BALB/c and C57BL/6 male mice (8-week-old) were randomly separated into: Control; Cisplatin (7.5 mg/Kg); Dexamethasone (2.0 mg/Kg); and Dexamethasone plus Cisplatin (2.0 mg/Kg of dexamethasone 1-hour prior to 7.5 mg/Kg of cisplatin). Drugs were administered intraperitoneally for three days. Body weight and food intake were evaluated on 2nd day. Alternating Current Biosusceptometry technique was employed to measure gastric contractions on 3rd day. Afterward, mice were killed for gastric histomorphometric analysis. Cisplatin decreased food intake and caused bradygastria in BALB/c mice; however, the amplitude of gastric contractions decreased in both BALB/c and C57BL/6. Dexamethasone and cisplatin combined restored the gastric frequency and food intake only in BALB/c, but drug combination reduced the gastric amplitude of contractions in both strains. Dexamethasone alone increased gastric mucosa thickness in C57BL/6 and decreased muscular thickness in BALB/c. In conclusion, the mouse strains presented differences in acute effects of cisplatin and dexamethasone alone and combined on gastric function. This reinforces the importance of choosing the appropriate mouse strain for studying the acute effects of drugs on the gastrointestinal tract.
Asunto(s)
Animales , Masculino , Ratones , Tracto Gastrointestinal/anomalías , Mucosa Gástrica/efectos de los fármacos , Estómago/anomalías , Dexametasona/efectos adversos , Cisplatino/agonistas , Ratones Endogámicos BALB C/clasificaciónRESUMEN
Abstract Faced with the increase of type 2 Diabetes mellitus (DM2) and the failure in treatment, questions have been raised about the clinical situation of these patients. The present study analyzes the prevalence of hypertension and obesity in DM2 patients. Data were collected through interviews and anamnesis of 16 participants. After the meetings, in which capillary glycemia and blood pressure were measured, the participants received guidance about glycemic monitoring, blood pressure control and changes in lifestyle. Approximately 75% of the participants were women with average age of 65 years, 87.5% were sedentary, 18.75% smoked and/or used alcoholic beverages and none performed regular blood glucose monitoring. The initial blood glucose average was 148 mg/ dL and finally decreased to 133 mg/dL. There was no significant difference in blood pressure levels. Regarding the body mass index, 89.4% of the patients were above normal standards and 100% had altered waist circumference values. There is a need for studies like this in order to promote educational practices for health and disease control, highlighting the importance of multidisciplinary teams and the pharmaceutical professional, since non-adherence to blood glucose monitoring, also associated with hypertension and obesity, can interfere with the individual's clinical condition.