RESUMO
BACKGROUND: The intestinal microbiota is involved in many physiological processes. However, the effects of microbiota in metabolic programming still unknow. We evaluated whether the transplantation of fecal microbiota during early life can program health or disease during adulthood in a model of lean and obese male and female Wistar rats. METHODS: Parental obesity were induced using a small litter (SL, 3 pups/dam) model. At 90 d old, normal litter (NL, 9 pups/dam) and SL males and females (parents) from different litters were mated: NL male vs. NL female; SL male vs. SL female. After birth, male and female offspring rats were also standardized in normal litters or small litters . From the 10th until 25th d of life, the NL and SL male and female offspring received via gavage of a solution containing the diluted feces of the opposite dam (fecal microbiota, M) or saline solution (S). At 90 d of age, biometric and biochemical parameters were assessed. RESULTS: NLM male rats transplanted with obese microbiota showed increased body weight, and fat pad deposition, hyperinsulinemia, glucose intolerance and dyslipidemia. SLM male rats transplanted with lean microbiota had decreased retroperitoneal and mesenteric fat, triglycerides and VLDL levels and improvement of glucose tolerance. Despite SLM female rats showed higher visceral fat, microbiota transplantation in female rats caused no changes in these parameters compared with control groups. CONCLUSION: Fecal microbiota transplantation during lactation induces long-term effects on the metabolism of male Wistar rats. However, female rats were resistant to metabolic alterations caused by the treatment.
Assuntos
Transplante de Microbiota Fecal , Lactação , Tecido Adiposo/metabolismo , Animais , Animais Recém-Nascidos , Peso Corporal , Feminino , Masculino , Obesidade/metabolismo , Obesidade/terapia , Ratos , Ratos WistarRESUMO
Exercise counteracts obesity effects, but information on how early-life obesity may affect long-term adaptation to exercise is lacking. This study investigates the impact of early-life postnatal overfeeding (PO) on animals' adaptation to exercise. Only male Wistar rats were used. On postnatal day (PN) 30, rats from control (NL-9 pups) or PO (SL-3 pups) litters were separated into four groups: NL-sedentary (NL-Se), NL-exercised (NL-Ex), SL-sedentary (SL-Se), and SL-exercised (SL-Ex). Exercised groups performed moderate-intensity exercise, running on a treadmill, from PN30 to PN90. Further experiments were carried out between PN90 and PN92. PO promoted obesity in SL versus NL rats (P < 0.05). Exercise reduced body weight (P < 0.001), body fat (P < 0.01), and improved glucose homeostasis in SL-Ex versus SL-Se. SL-Ex presented lower VO2max (P < 0.01) and higher post-exercise LDH (P < 0.05) compared to NL-Ex rats. Although moderate exercise counteracted obesity in SL rats, early-life overnutrition restricts fitness gains in adulthood, indicating that early obesity may impair animals' adaptation to exercise.
Assuntos
Hipernutrição , Animais , Animais Recém-Nascidos , Peso Corporal , Masculino , Músculos , Obesidade/etiologia , Hipernutrição/complicações , Ratos , Ratos WistarRESUMO
Overweight/obesity has become a worldwide epidemic, and factors such as a sedentary lifestyle and inadequate eating habits directly contribute to the development of this condition. Studies indicate that rapid weight gain at critical development stages, such as the lactation period, is associated with the development of obesity, cardiovascular diseases, and diabetes in the long term. In addition to metabolic changes during adulthood, overweight/obesity may influence reproductive function of the population. In this context, the present study aimed to evaluate postnatal overfeeding effects on male and female Wistar rat reproductive parameters. Postnatal overfeeding was induced by applying the litter reduction method for both sexes. Forty animals were used, divided into four groups: two with normal litters (NLâ and NLâ) and two with small litters (SLâ and SLâ). The males were euthanized at 90 days of age, on the same date the females were mated. Females were also euthanized after the 20-day gestation. Metabolic and reproductive variables were analyzed. Regarding males, SL animals showed increased body weight, adiposity, and decreased relative weight of the seminal vesicle, prostate, and epididymis as well as changes in the ITT and OGTT glycemic tests. Concerning females, SL animals presented increased body weight, relative perigonadal fat weight, glucose intolerance as well as modify the vaginal opening and increased weight of female pup. The litter reduction method was efficient in leading to metabolic and reproductive alterations in male and female Wistar rat.
Assuntos
Peso Corporal , Obesidade/etiologia , Ovário/fisiologia , Hipernutrição/fisiopatologia , Reprodução , Testículo/fisiologia , Aumento de Peso , Animais , Animais Recém-Nascidos , Feminino , Teste de Tolerância a Glucose , Insulina/metabolismo , Lactação , Masculino , Ovário/citologia , Ratos , Ratos Wistar , Testículo/citologiaRESUMO
AIMS: Obesity is associated with innumerous comorbidities, including cardiovascular diseases, that occur by various mechanisms, including hyperactivation of the renin angiotensin system, oxidative stress and cardiovascular overload. Postnatal early overfeeding (PO) leads to metabolic imprinting that induces weight gain throughout life, and in this paper, we aimed to evaluate cardiovascular parameters and cardiac molecular changes due to obesity induced early in life by PO. MAIN METHODS: Male Wistar rats (120-days-old), raised in normal (NL) or small litters (SL), were submitted to cardiac assessment by transthoracic echocardiography and blood pressure evaluation. Thereafter, the hearts and aorta rings from these animals were submitted to ex-vivo isolated assays. Still, cardiac morphological and molecular analyses were performed. KEY FINDINGS: PO induced ventricular hypertrophy, raised blood pressure, increased fibrosis, and ex-vivo cardiac dysfunction in the SL group. Furthermore, SL animals presented impaired vascular relaxation and increased vascular constriction responses. Besides functional alterations, SL animals presented augmented RAB-1b and SOD-1, despite no changes in RAS receptors expression or Akt/eNOS pathway. SIGNIFICANCE: Taken together, our results consolidate the knowledge that the PO during lactation is critical for cardiometabolic programming, leading to oxidative stress and cardiac remodeling in later stages of life.
Assuntos
Sistema Cardiovascular/fisiopatologia , Obesidade/fisiopatologia , Hipernutrição/fisiopatologia , Animais , Animais Recém-Nascidos/metabolismo , Peso Corporal , Doenças Cardiovasculares/etiologia , Modelos Animais de Doenças , Coração , Masculino , Miocárdio/citologia , Miocárdio/metabolismo , Obesidade/complicações , Hipernutrição/complicações , Estresse Oxidativo/fisiologia , Ratos , Ratos Wistar , Remodelação Vascular/fisiologia , Aumento de PesoRESUMO
PURPOSE: The early-life nutritional environment affects long-term glucose homeostasis, we investigated the effects of maternal low-protein diet combined with postnatal early overfeeding on the male offspring's glucose homeostasis in adulthood. METHODS: Only male rats were used, and their delivery was considered postnatal-day 0 (PN0). Wistar rats' dams were divided into control (NP) or low-protein diet (LP). LP dams remained on the diet until PN14, after which all animals were supplied with the control diet. At PN2, litters were adjusted to 9 (control-NL) or 3 (postnatal-overfeeding-PO) pups, resulting in four experimental groups: NP-NL, NP-PO, LP-NL, and LP-PO. Litters were weaned on PN21. At PN80, a batch of animals from all experimental groups underwent surgery for cannula implantation, followed by intravenous glucose tolerance test (ivGTT), but the insulinogenic index (ISI) was calculated. At PN81, animals were euthanized and tissues were collected. RESULTS: LP-diet and early postnatal-overfeeding were effective in promoting the expected biometric outcomes at PN21 and PN81, but the LP-PO animals present a biometric profile similar to the control (NP-NL) group. Postnatal-overfeeding increased fasting glycemia in LP-PO animals (p < 0.01). In the ivGTT, postnatal-overfeeding elevated the glycemia (p < 0.0001), exacerbated in LP-PO animals (p < 0.0001). Insulinemia was reduced by both, maternal LP-diet and postnatal-overfeeding, with a higher degree of reduction in LP-PO animals (p < 0.0001). Maternal LP-diet and postnatal-overfeeding reduced the ISI (p < 0.0001). Factors interaction lead the LP-PO to a lower ISI compared to all other groups (p < 0.0001). CONCLUSIONS: The combination of low-protein diet in breastfeeding dams with postnatal overfeeding disturbed the offspring's glucose metabolism in adulthood.
Assuntos
Glicemia/metabolismo , Dieta com Restrição de Proteínas/efeitos adversos , Hiperfagia/complicações , Lactação , Animais , Animais Recém-Nascidos , Ingestão de Alimentos , Feminino , Teste de Tolerância a Glucose , Homeostase , Insulina/sangue , Masculino , Fenômenos Fisiológicos da Nutrição Materna , Ratos , Ratos WistarRESUMO
AIM: In this study, the effects of postnatal overfeeding on heart energy homoeostasis and cardiac haemodynamics in adult male Swiss mice were examined. METHODS AND RESULTS: During the suckling period, the mice were divided into four groups of control or overfed pups in combination with baseline or ischaemia/reperfusion treatments (control group baseline, CGBL; overfed group baseline, OGBL; control group ischaemia/reperfusion, CGIR; and overfed group ischaemia/reperfusion, OGIR). End diastolic pressure (EDP), heart contraction speed (Max dP/dt), relaxation speed (Min dP/dt), isovolumetric relaxation time (Tau) and frequency by beats per minute (BPM) were measured. During baseline and ischaemia/reperfusion, key proteins such as AKT1, AKT2, AKT3, pAKT, adenosine monophosphate-activated protein kinase (AMPK), pAMPK, insulin receptor beta (IRß), protein tyrosine phosphatase 1B (PTP1B), insulin receptor substrate 1 (IRS1), fatty acid binding protein (FABP), CD36, phosphoinositide 3-kinase (PI3K) and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α) were studied. The expression of atrial natriuretic peptide (ANP), B-type natriuretic peptide (BNP), carnitine palmitoyltransferase 1 (CPT1) and uncoupling protein 3 (UCP3) was studied as a marker of cardiac hypertrophy and energetic metabolism. Cardiac fibrosis was analyzed by quantifying collagen deposition, which is increased in the OGBL and OGIR groups compared with the control groups. CONCLUSIONS: The OGBL group showed reduced EDP compared with the CGBL group and high Max dP/dt compared with the OGBL group. Ischaemia/reperfusion increased EDP and Min dP/dt in the intragroup comparison. By contrast, Tau and frequency were not significantly different among groups. The OGIR mice showed significant alterations in heart metabolism proteins, including AKT2, pAKT/AKT1, pAKT/AKT2, AMPK, pAMPK/AMPK, PTP1B, IRS1, FABP and CD36. Furthermore, alterations in ANP, BNP, CPT1 and UCP3 messenger RNA (mRNA) expression indicated hypertrophy and reduction in their efficiency, such that exclusive overnutrition in childhood induces a long-term effect on haemodynamics, metabolism and heart remodelling.