Omega3-polyunsaturated fatty acid ameliorates metabolic disorders in adulthood rats caused by postnatal early overfeeding / 中华内分泌代谢杂志

Objective@#To explore the effect and mechanism of omega 3-polyunsaturated fatty acid(ω3-PUFA) dietary intervention on mitochondrial function of white adipose tissue in adult rats with postnatal early overfeeding.@*Methods@#An overfed animal model by adjusting litter size was developed for the study of neonatal overfeeding. The litter size was adjusted to 3 male rats per litter(small litter, SL group) and 10 pups per litter(normal litter, NL group). After weaning(week 3), the pups were fed standard chow or ω3-PUFA diet(SL-FO) until postnatal weeks 13. Food intake, body weight, and rectal temperature of rats were measured regularly, and energy metabolism of animals was monitored in week 13. During week 3 and 13, subcutaneous adipose tissue was collected. Inguinal preadipocytes of mice were isolated and induced to differentiate, and 50 μmol/L eicosapentaenoicacid(EPA) was administered for 48 h at the late stage of differentiation. The mRNA and protein expression levels of mitochondrial related genes, mitochondrial copy number, and oxygen consumption rate of adipocytes were detected in adipose tissue and adipocytes.@*Results@#By the 3rd week, the body weight, food intake, and fat cell area in SL group were higher than those in NL group while the body temperature was lower until to 13 weeks. By the 13th week, the O2 consumption, CO2 output, and heat production of rats in SL group were lower than those in NL group. Meanwhile, the expressions of mitochondrial function related genes such as uncoupling protein 1(UCP1), carnitine palmitoyltransferase 1(CPT1), SIRT1, and mitochondrial biosynthesis regulatory gene peroxisome proliferator-activated receptor coativator-1 (PGC1α) in adipose tissue by the 3rd and 13th week were significantly reduced(P<0.05). After weaning, ω3-PUFA diet significantly reduced weight gain in SL rats, increased UCP1 protein expression, restored energy metabolism level and mitochondrial function related gene expression. In vitro intervention of EPA increased the mitochondrial copy number, the mRNA and protein expression levels of mitochondrial biosynthesis and functional genes, as well as the mitochondrial basic oxygen consumption rate(P<0.05).@*Conclusion@#ω3-PUFA improves postnatal overfeeding-induced impairment of the mitochondrial function and biosynthesis of subcutaneous white adipose tissue in rats, which may be an important mechanism for fish oil diet to inhibit the early over-nutrition program and restore the thermogenic metabolism.

Effects of overfeeding in breastfeeding period on blood pressure and vascular endothelial dilation function of rats / 中华临床营养杂志

Objective To study the effects of postnatal overfeeding and high-fat diet on blood pressure of rats,and to explore the pathophysiological mechanism underlying hypertension induced by continuous early postnatal overfeeding.Methods Male Sprague-Dawley rats were randomly divided into normal feeding group (10/litter) and overfeeding group (3/litter) on postnatal day 3 with a random number table.After weaning at postnatal week 3,the rats were randomly given standard chow or high-fat (HF) diet until week 16.Hence four groups were analyzed,namely normal feeding group,breastfed overfeeding group,post-weaning overfeeding group,and continuous overfeeding group.Body weight was continuously monitored in each week.Visceral fat pad (retroperitoneal and perigenital),systolic pressure,and heart rate were observed at week 3 and week 16.Thoracic aorta was sampled for measurement of vascular endothelial dilation function.Histological morphology was observed with HE staining,nitric oxide content of thoracic aorta was detected with nitrate reductase method.The mRNA expression of endothelial nitric oxide synthase (eNOS) in thoracic aorta was determined by real-time polymerase chain reaction.The protein expressions of eNOS and phosphorylated eNOS were determined by Western blot.Results At week 3,breastfed overfeeding rats displayed significantly larger body weight [(77.80 ± 0.57) g vs.(62.80 ±0.85) g,t =14.576,P ＜ 0.01] and visceral fat [retroperitoneal:(8.19 ± 0.49) mg/g vs.(4.92 ± 0.31) mg/g,t =5.629,P＜0.01;perigenital:(3.50 ±0.29) mg/g vs.(2.08 ±0.13) mg/g,t =4.552,P ＜0.01] compared with normal feedindg rats,and the protein expression of phosphorylated eNOS in aortic tissues was significantly reduced to week 16 (F =15.215,P ＜0.01);high-fat diet feeding after weaning further increased the body weight and fat mass in breastfed overfeeding rats.At week 16,continuous overfeeding rats showed hypertension [(149 ± 1.94) mmHg (1 mmHg =0.133 kPa),F =22.834,P ＜0.01],impaired vascular endothelial dilation function (F =7.648,P ＜ 0.05),and reduced protein expression of phosphorylated eNOS (F =15.215,P ＜ 0.01),while the post-weaning overfeeding group only had elevated blood pressure.Conclusions Overfeeding in breastfeeding period and high-fat diet after weaning leads to hypertension.The continuous decrease in phosphorylated eNOS in vascular tissues may be an important molecular process participating in the occurrence of vascular endothelial dysfunction in adults induced by postnatal overfeeding.

Estilos de apego y su relación con el patrón alimenticio de restricción-sobrealimentación en sujetos dietantes crónicos / Styles of attachment and its relations to food bosses of restriction – overfeeding in individuals chronic dieters

La sociedad establece la delgadez como estereotipo de belleza, éxito y felicidad generando insatisfacción corporal y preocupaciones por el peso, lo que lleva a los sujetos a realizar múltiples tipos de dietas. Esta restricción crónica, en vez de reducir el peso, genera sobreingesta de alimentos. Ante situaciones de estrés y ansiedad los dietantes crónicos utilizan la restricción-sobrealimentación como una estrategia de regulación afectiva. El objetivo de la presente investigación fue explorar el patrón de restricción alimentaria y su relación con los estilos de apego en una muestra de sujetos dietantes crónicos de la ciudad de San Luis. La muestra quedó conformada por 65 individuos, de ambos sexos, cuyas edades oscilaron entre los 20 y 40 años. Se aplicó la Escala Revisada de Restricción Alimentaria (ERA) (Silva, 2010) y la Escala de Estilos de Apego (Casullo & Fernández Liporace, 2005). En relación a los resultados obtenidos, se encontró que más de la mitad de los individuos encuestados presentaban características que los definían como dietantes crónicos, manifestando un marcado interés por realizar distintos tipos de dietas y en controlar la ingesta cotidiana. Además, la presencia de estilos de apego temeroso-evitativo y ansioso en dietantes crónicos podría estar propiciando la aparición y mantenimiento de un patrón alimentario de restricción sobrealimentación...

The society establishes the thinness as stereotype of beauty, success and happiness generating corporal dissatisfaction and worries for the weight, which leads to the subjects to realizing multiple types of diets. This chronic restriction generates instead of the food excess of Food reduces the weight. Before situations of stress and anxiety the chronic dieters cause the restriction – excess of alimentation as a strategy of affective regulation. The lens of the present research was to explore of food restriction in a sample of subjects of San Luis' city and his relation with the style of attachment. The sample remained shaped by 65 individuals of both gender sexes which ages ranged between 20 and 40 years. It applied the Scale Checked of Food Restriction (ERA) (Silva, 2010) and the Scale of Styles of Attachment (Casullo & Fernandez Liporace, 2005). In relation to the obtained results, one found great quantity of subjects that present characteristics that define them like chronic dieters demonstrating a marked interest to realize different types of diets and in controlling the daily ingestion. Aside from the presence the styles of fearful attachment - avoid and anxious in these individuals, it would be favoring the appearance and maintenance of a food boss of restriction – excess of alimentation...

Neonatal Overfeeding Induced by Reducing the Litter Size Leads to an Obese Phenotype and Increases Preference for Sweet Food in Adult Male Rats.

Aim: the aim of this study was to induce obesity in rats using the neonatal overfeeding protocol and evaluate in adult male animals standard chow intake, sweet food intake, the preference between sweet food and standard chow, locomotor activity and anxiety-like behavior. Methodology: The neonatal overfeeding protocol consisted of reducing the litter size to 4 animals (small litters = SL) compared to 8 animals in normal litters (NL). In these experiments we used 55 offspring from 18 litters. Results: obesity was successfully induced as observed by increased body weight and depots of abdominal fat in SL animals compared to NL; [F(1, 53)=15.018; P<.001] for body weight and [t(48.06)=2.186 P=.03] for abdominal fat.No difference between groups was found in standard chow [t (16)=1.843 P=.08] and sweet food intake [t(53)=0.453 P=.65], however in the test that evaluated the preference between both foods SL animals consumed more sweet food than NL [t(48) =2.481 P=.02]. Additionally, there was no difference between groups regarding locomotor activity [t(52)=0.073 P=.94] but SL animals showed reduced anxiety-like behavior compared to NL [t(39.36)=2.205 P=.03]. Conclusion: this study supports the use of neonatal overfeeding protocol as a model of early obesity and showed for the first time the increased preference for sweet food in adult neonatal overfed animals.

Effect of omega-3 polyunsaturated fatty acids diets after early over-feeding on expressions of ghrelin in gastric tissue and leptin in serum in adult rats / 中华临床营养杂志

Objective To observe ghrelin expression in gastric tissue and serum leptin level of the early over-fed rats given ω-3 polyunsaturated fatty acids (PUFAs) diets after weaning,and explore the effects of early over-feeding and diets intervention on the metabolic syndrome in adult rats.Methods Male Sprague-Dawley rats were divided into normal feeding group (NF group,10 per litter) or over-feeding group (OF group,3 per litter) in postnatal day 3,and then different diets were given after weaning (postnatal day 21).The OF group was separately given conventional diet (OF + Con group),high-fat diet (OF + HF group),or ω-3 PUFAs (OF + ω-3 group) ; while the NF group was separated into NF + Con group and NF + HF group.Body weight and food intake were recorded every week.In week 6 and week 16,glucose tolerance test was perforfmed.Serum leptin,ghrelin,and triglyceride were assayed by enzyme-linked immuno-absorbent assay.Ghrelin mRNA and protein levels in gastric tissue were quantified by real-time PCR and immunohistochemistry.Results At week 16,energy intake,body weight and glucose intolerance in OF + HF group were significantly higher than in NF + HF group (t =-3.453,P =0.014 ; t =-6.406,P =0.000 ; F =16.249,P =0.000),and serum triglycerides,ghrelin mRNA of gastric tissue were significantly higher than those of OF + Con group (t =4.72,P =0.005 ; t =8.486,P =0.000).At week 16,the serum leptin level in OF + Con group was higher than that in NF + Con group (t =-3.274,P =0.031),also higher in OF + HF group than that in OF + Con group (t =3.028,P =0.014).There were no significant differences in serum ghrelin and the area of ghrelin immuno-positive cells in the gastric tissue among groups.The above indicators in OF + ω-3 group were not different from those of NF + Con group.Conclusions Over-feeding during the lactation period may lead to high susceptibility to obesity and disordered glucose and lipid metabolism.It can also increase serum leptin and ghrelin mRNA expression in gastric tissue,aggravate leptin resistance and feeding control disorders.Dietary ω-3 PUFAs offered protection against excessive accumulation of adipose tissue,glucose intolerance,leptin resistance,and maintained normal levels of leptin and ghrelin.

Influência da grelina sobre o processo de estímulo-secreção de insulina in vitro em camundongos Swiss adultos hiperalimentados na lactação / Ghrelin influence on the process of insulin secretion stimulus-vitro in mice Swiss adults overfeeding in lactation

O excesso ou a privação de nutrientes em períodos específicos do desenvolvimento, tais como a lactação, estimulam alterações no metabolismo celular, por exemplo. Estas modificações perpetuam-se ao longo da vida e em conseqüência tornam o organismo mais suscetível ao aparecimento de patologias na idade adulta (Programação Metabólica). Estudamos a influência da grelina na secreção de insulina em camundongos Swiss de 120 dias submetidos à hiperalimentação na lactação. Para induzir a hiperalimentação as ninhadas foram reduzidas a 3 filhotes machos por lactante no 3o dia de vida pós-natal. As ninhadas controle foram ajustadas para 9 filhotes machos por lactante. Na idade adulta os animais hiperalimentados (AH) exibiram em comparação aos animais controle (AC) um incremento de 20% no peso corporal, maior índice de Lee (1705,63 g/mm + 29,3 vs 1374,10 g/mm + 54,9; p< 0,001), elevação da gordura corporal (31,0% + 4,6 vs 21,5% + 3,6; p< 0,01), aumento da gordura retroperitoneal (0,79 g + 0,1 vs 0,44 g + 0,1; p< 0,001), hiperglicemia de jejum (151,83 mg/ dl + 8,3 vs 118,0 mg/ dl + 1,0; p< 0,001), hiperinsulinemia de jejum (54,06 µUI/ml + 2,3 vs 19,28 µUI/ml + 1,53; p< 0,001) e hipogrelinemia de jejum (98,64 pg/ml + 56,5 vs 201,14 pg/ml + 46,4; p< 0,05). Os AH apresentaram maior secreção de insulina in vitro em presença de glicose aos 10 minutos (209,66 µUI/ml + 46,5; p< 0,05), 30 minutos (441,88 µUI/ml + 30,2; p< 0,05) e 60 minutos (214,34 µUI/ml + 29,8) em comparação aos AC, respectivamente 86,90 µUI/ml + 9,5; 74,31 µUI/ml + 7,7 vs 27,45 µUI/ml + 6,1; p< 0,05. As ilhotas pancreáticas dos AH adultos demonstraram em relação aos AC diminuição do consumo de O2 (1,76 pmols O2/ s. ilhota-1 + 0,4 vs 4,85 pmols O2/ s. ilhota-1 + 1,5; p< 0,001) e elevação do conteúdo do receptor de grelina GHSR1A (3,05 % + 2,13 vs 0,95 % + 0,1; p< 0,05)...

Excess or lack of nutrients at specific times of development generates adaptive responses that can change the body causing the onset of chronic diseases in adulthood (Metabolic Programming). We studied the influence of the hormone ghrelin in insulin secretion of adult Swiss mice overfed during lactation. To induce early postnatal overnutrition, the litter size was reduced to 3 pups per litter at the 3rd day after birth. In the control group, the litter size was adjusted to 9 pups per litter. In adulthood, overfed group (OG) had an increase of 20% in body weight compared to control group (CG). OG had increased in Lee index (1705.63 g/mm + 29.3 vs 1374.10 g/mm + 54.9; p< 0.001), high body fat (31.0% + 4.6 vs 21.5% + 3.6; p< 0.01), and an elevated retroperitoneal fat (0.79 g + 0.1 vs 0.44 g + 0.1; p< 0.001), fasting hyperglycemia (151.83 mg/ dl + 8.3 vs 118.0 mg/ dl + 1.0; p< 0.001), high fasting insulinemia (54.06 µUI/ml + 2.3 vs 19.28 µUI/ml + 1.53; p< 0.001), and low fasting plasma ghrelin (98.64 pg/ml + 56.5 vs 201.14 pg/ml + 46.4; p< 0.05) compared to CG at 120 days. OG exhibited high insulin secretion in vitro at 10 minutes (209.66 µUI/ml + 46.5), 30 minutes (441.88 µUI/ml + 30.2), and 60 minutes (214.34 µUI/ml + 29.8) compared to CG, respectively 86.90 µUI/ml + 9.5; 74.31 µUI/ml + 7.7 vs 27.45 µUI/ml + 6.1; p< 0.05. Pancreatic islets from OG had a decrease of O2 consumption compared to CG (1.76 pmols O2/ s. islets-1 + 0.4 vs 4.85 pmols O2/ s. islets-1 + 1.5; p< 0.001) and an increased of GHSR1A content (3.05 % + 2.13 vs 0.95 % + 0.1; p< 0.05). Acylated ghrelin increased control group’s insulin secretion in vitro at 30 minutes (CG with ghrelin: 208.50 µUI/ml + 40.85 vs CG without ghrelin 74.31 µUI/ml + 7,7; p< 0.05) and decreased the respiratory control ration (CG with ghrelin: 1.45 + 0.2 vs CG without ghrelin: 2.51 + 0.7; p< 0.05)...

Effects of chronic treadmill training on body mass gain and visceral fat accumulation in overfed rats

This study evaluated the effects of chronic treadmill training on body mass gain and visceral fat accumulation in overfed rats. Overfeeding was induced by reducing the litter size to 3 male pups per mother during the suckling period. The litter size of control rats was adjusted to 10 male pups per mother. Seven weeks after birth overfed and normally fed rats were selected and assigned to a sedentary protocol or to a low-intensity treadmill training protocol (60 min, 5 times/week, for 9 weeks). Four groups (overfed sedentary, N = 23; normally fed sedentary, N = 32; overfed exercised, N = 18, and normally fed exercised, N = 18) were evaluated at 18 weeks. Data are reported as means ± SEM. Initial body weight was similar in control and overfed rats [8.0 ± 0.2 g (N = 42) vs 8.0 ± 0.1 g (N = 50); P > 0.05] and body weight gain during the suckling period was higher in the overfed rats (30.6 ± 0.9 vs 23.1 ± 0.3 g; P < 0.05). Exercise attenuated the body weight gain of overfed compared to sedentary rats (505 ± 14 vs 537 ± 12 g; P < 0.05). The sedentary overfed rats showed higher visceral fat weight compared to normally fed animals (31.22 ± 2.08 vs 21.94 ± 1.76 g; P < 0.05). Exercise reduced visceral fat by 36.5 percent in normally fed rats and by 35.7 percent in overfed rats. Exercise attenuated obesity in overfed rats and induced an important reduction of visceral fat.

Análise da expressão de TNF-alpha e CD133 no pâncreas após o transplante de células de medula óssea em camundongos hiperalimentados durante a lactação / Analysis of TNF-alpha and CD133 in pancreas after transplantation of bone marrow cells in overfeeding mice during lactation

Estudos populacionais, assim como modelos animais demonstram que além dos fatores já conhecidos, como uma dieta não balanceada e sedentarismo, insultos nutricionais no período gestacional ou durante a lactação, causam alterações metabólicas importantes que levam ao surgimento da obesidade, Diabetes Mellitus tipo 2 (DM2) e doenças cardiovasculares em longo prazo. Nesse estudo, analisamos o pâncreas de camundongos hiperalimentados adultos (150 dias) e camundongos hiperaliemntados jovens (21 e 28 dias). Os camundongos hiperalimentados de 21 dias receberam transplante de células mononucleares de medula óssea (CMO) e o resultado desse transplante foi observado aos 28 dias, quando os animais foram sacrificados. Nós investigamos: a apoptose das células beta através do fator pró-apoptótico Bax; a proliferação das células da ilhota pancreática através do antígeno nuclear de proliferação celular (PCNA); a expressão da citocina TNF-alpha, relacionado com a resistência à insulina em animais obesos e a expressão de células tronco CD133 com o objetivo de estudar a participação dessa célula na renovação da massa de células beta durante o estabelecimento da DM2. As análises das proteínas citadas no pâncreas foram realizadas através de microscopia de luz, microscopia confocal, microscopia eletrônica e Western blotting. O peso dos animais, a morfometria das ilhotas pancreáticas, bem como os níveis de glicose e insulina plasmáticos também foram determinados. Nossos resultados confirmaram que os camundongos hiperalimentados adultos apresentavam elevados níveis de glicose e insulina plasmática quando comparados ao grupo controle. Além disso, camundongos hiperalimentados adultos apresentaram aumento na expressão de Bax, indicando apoptose das células beta, maior expressão de TNF-alpha nas ilhotas pancreáticas, e presença de células CD133 nas ilhotas e ductos pancreáticos de camundongos hiperalimentados. Ao analisarmos os animais com 21 dias também observamos elevados níveis...

Population studies as well as animal models show that besides the factors already known as an unbalanced diet and sedentary lifestyle, nutritional insults during pregnancy of during lactation, causes important metabolic changes that lead to the emergence of obesity, type 2 diabetes mellitus (DM2) and cardiovascular diseases in long-term. In this study, we analyzed the pancreas of overfed adult mice (150 days) and young mice (21 and 28 days). At day 21, overfed mice were transplanted with bone marrow mononuclear cells (BMCs) and the results of this transplantation were observed at day 28. We investigated beta-cell apoptosis through pro-apoptotic factor Bax, the proliferation of pancreatic islet cells by proliferating cell nuclear antigen (PCNA), expression of TNF-alpha which has been linked to insulin resistance in obese animals and the expression of CD133 stem cells, in order to study the participation of this cell on the recovery of beta-cell mass during the establishment of DM2. The protein analysis, were performed using light microscopy, confocal microscopy, electron microscopy and Western blotting. The animals weight, morphology of pancreatic islets, as well as plasma levels of glucose and insulin were also determined. Our results confirmed that adult overfed mice had high levels of blood glucose and insulin when compared to control mice. Moreover, overfed adult mice showed an increased expression of Bax, indicating apoptosis of beta cells, also confirmed by transmission electron microscopy, increased expression of TNF-alpha in pancreatic islets when compared with the control group, and interestingly we observed the presence of CD133 cells in the pancreas of overfed mice. By analyzing the animals with 21 days, we also observed high levels of blood glucose and insulin in the overfed group, but we did not observe Bax expression at this lifetime. The expression of TNF-alpha was also increased in pancreas of overfed mice at day 21...

Efecto de la Sobrealimentación sobre las Características de la Canal y la Degradación Postmortem de la Vinculina y Troponina-T en Carne de Novillos Doble Propósito / Overfeeding Effects on Beef Carcass Traits and Postmortem Degradation of Vinculin and Troponin-T in Dual Purpose Steers

El efecto de sobrealimentación sobre las características de la canal y la degradación de la vinculina y la troponina-T a tres tiempos postmortem (0, 24 y 48 h), fue evaluado en 10 novillos doble propósito de 21 m de edad. Los animales fueron segregados al azar en dos tratamientos durante 12 m, como sigue: Tratamiento 1 (T1): cinco (5) novillos (grupo testigo) alimentados con heno (Cynodon nlemfuensis), más 20% de concentrado (relación heno:concentrado = 80:20, para una ganancia diaria de peso (GDP) de 100 g/d). Tratamiento 2 (T2): cinco (5) novillos alimentados con heno (Cynodon nlemfuensis), más 40% de concentrado (relación heno: concentrado = 60:40, para una GDP de 500 g/d). Las canales fueron evaluadas, para las características cualitativas y cuantitativas a las 24 h postmortem. Para evaluar la degradación de vinculina y troponina-T mediante la técnica de Western Blot, se colectaron 0,5 g del músculo longissimus dorsi de cada media canal al beneficio (0, 24 y 48 h postmortem). El análisis de varianza(ANAVAR) incluyó el peso de los animales al inicio del ensayo como covariable. Los resultados indicaron que las canales de los novillos sobrealimentados mejoraron sus características en canal, presentando mayor área del ojo costal, mayor espesor de grasa y mayor madurez ósea (P<0,05), sin alcanzar niveles adecuados de acabado de grasa. Se observó que la sobrealimentación no varió el patrón de degradación de la vinculina y la troponina-T a ningún tiempo postmortem. La vinculina se degradó a partir de las 24 h postmortem; sin embargo, no se detectó degradación de la troponina-T. Estos resultados deben ser confirmados con un número mayor de animales junto con la evaluación cuantitativa de la expresión de las proteínas.

The effect of overfeeding on carcass characteristics and on degradation of vinculin and troponin-T at three different postmortem times (0, 24, and 48 h) were evaluated in dual purpose steers. A total of 10 steers, 21 months of age was used. The animals were randomly selected and allocated to two different treatment protocols for 12 months, as follows: Treatment 1 (T1): Five steers (Control Group) fed with a diet consistent of hay (Cynodon nlemfuensis) plus concentrate, with a hay/concentrate ratio of 80:20, to reach a daily weight gain (DWG) of 100 g/d; Treatment 2 (T2); five steers fed with hay (Cynodon nlemfuensis) plus concentrate with a hay/concentrate ratio of 60:40, to obtain a DWG of 500 g/d. Carcasses were assessed for both qualitative and quantitative characteristics at 24 h postmortem. To evaluate the degradation of vinculin and troponin-T at three different times (0, 24, and 48 h postmortem), 0.5 g of the longissimus dorsi muscle was collected from each half carcass and subjected to a Western blot analysis. Samples were analyzed by ANOVA. The analysis included the weight of the animals as a covariance. The results of the present investigation indicate that the carcasses of overfed steers exhibited better carcass traits, showing larger loin eye areas, back fat thickness, and a skeletal maturity (P≤0.05), without reaching adequate levels of fat finish. It was also observed that overfeeding did not change the pattern of degradation of vinculin and troponin-T at any postmortem time. Vinculin showed degradation at 24 h postmortem while troponin-T was not degraded. These results must be confirmed using a greater number of animals and a quantitative evaluation of protein expression.

Efeitos da hiperalimentação no início da vida sobre a programação dos metabolismos sistêmico e cardíaco dos filhotes / Effects of overfeeding in early life on the programming of systemic and cardiac metabolism of offspring

Introdução: Estudos populacionais e investigações em modelos animais demonstraram que um ambiente perinatal adverso, incluindo a hipernutrição materna, está associado com consequências metabólicas em longo prazo, particularmente a obesidade, a Diabetes Mellitus tipo 2 (DM2) e as doenças cardiovasculares. No presente estudo, nós primeiro investigamos a associação entre a hiperalimentação através da redução da ninhada com alterações nas cascatas de sinalização da insulina e da leptina nos corações de ratos Wistar no início da vida. Em um segundo momento, nós investigamos adaptações metabólicas, genéticas e cardíacas nas proles de camundongos C57BL/6J, cujos pais foram alimentados com uma dieta hiperlípidica (DH) antes do acasalamento, e cujas mães permaneceram nesta mesma dieta durante a gestação e a lactação. Métodos: Para a primeira parte do nosso estudo, ratos Wistar machos foram hiperalimentados através da redução da ninhada para apenas 3 filhotes. Aos 10 e 21 dias de vida, proteínas-chave como, os receptores de insulina e de leptina, a PI3-quinase, a JAK2, a STAT3 e o GLUT4 foram medidas por Western Blotting. Além disso, o peso dos filhotes, bem como os níveis plasmáticos de glicose, insulina e leptina foram determinados. Para a segunda parte do estudo, camundongos C57BL/6J foram alimentados por uma dieta controle ou por uma DH por 4 semanas antes do acasalamento, e as fêmeas grávidas foram mantidas nestas mesmas dietas até o desmame. Após o desmame, os filhotes foram alimentados ou com uma ração controle (PCC e PHC), ou com uma DH (PCH e PHH) por 9 semanas. Aos 3 meses, o metabolismo sistêmico, a função e o metabolismo cadíacos, bem como a expressão gênica foram investigados nos machos. Resultados: Ratos hiperalimentados através da redução da ninhada apresentaram sobrepeso, tiveram altos níveis plasmáticos de insulina e leptina, e um aumento no conteúdo cardíaco de todos os componentes das cascatas de sinalização da insulina e da leptina investigados...

Introduction: Population studies and investigations in animal models have shown that adverse peri-natal environments, including maternal overnutrition, are associated with long-term metabolic consequences, particularly obesity, insulin resistance, type 2 diabetes and cardiovascular diseases. In the present study, we first investigated the association between overfeeding through litter size reduction and alterations in insulin and leptin signaling in the hearts of Wistar rats at early life. At a separate occasion, we analyzed metabolic, genetic and cardiac adaptations in the male adult offspring of C57BL/6J mice, whose parents were fed a high-fat diet (HFD) before breeding, and whose mothers were kept in the HFD throughout gestation and lactation. Methods: For the first part of the study, Wistar rats were overfed through litter size reduction to only three pups. At 10 and 21 days of life, key proteins such as insulin receptor, leptin receptor, PI3-kinase, JAK2, STAT3, and GLUT4 were measured by Western Blot. Furthermore, the pups' weight and the plasma levels of insulin, leptin and glucose were determined. For the second part of the study, the parents were fed either control or HDF for 4 weeks before breeding, and the pregnant females were kept on the same respective diets until weaning. After weaning, the offspring were fed either normal chow (Control and PHF) or a HFD (Cont-HF and PHF-HF) for 9 weeks. At 12 weeks, systemic metabolic parameters, cardiac function and metabolism, and gene expression were investigated. Results: Rats overfed through litter size reduction were overweight, had high insulin and leptin plasma levels, and increased cardiac content of all components from insulin and leptin signaling cascades investigated, leading to an increased translocation of GLUT4 at 10 and 21 days of age. At 12 weeks, body weight, body fat and plasma levels of insulin, adiponectin and leptin were unchanged in PHF mice. Moreover, these mie had improved gluycose...