Intermittent food restriction upregulates critical hypothalamic genes involved in energy regulation imbalance.

The effect of intermittent food restriction (IFR) on the Central Nervous System is unclear, especially when alternated with an obesity-inducing diet (DIO). This study aimed to evaluate key genes involved in energy-regulation imbalance in the hypothalamus after IFR and DIO alternation. Therefore, 45-d-old female Wistar rats were divided into 4 groups: standard control (ST-C), fed with an ad libitum standard diet; DIO control (DIO-C), fed with a DIO in the first and last 15 d of the intervention and a standard diet between the 16th and 45th day; standard restricted (ST-R), fed with a standard diet in the first and last 15 d of the intervention followed by IFR at 50% of the ST-C diet between the 16th and 45th day; and DIO restricted (DIO-R), fed with a DIO in the first and last 15 d of the intervention and subjected to IFR under the same conditions as the ST-R group. At 105 d of age, animals were euthanized, and the hypothalamus was removed for quantitative polymerase chain reaction analysis. The ST-R and DIO-R groups showed higher inhibitor of nuclear factor kappa-B kinase subunit beta (P < 0.001; P = 0.029) and nuclear factor kappa B (P < 0.001; P = 0.029) gene expression when compared with the ST-C group. The same held true for the JNK (P = 0.001; P = 0.003) and PPARα genes (both P < 0.001). Instead, the DIO-R group exhibited higher CCL5 gene expression than the ST-C (P = 0.001) and DIO-C (P < 0.001) groups, whereas all groups had higher SOCS3 gene expression than did the ST-C group. These data together suggest that IFR, whether combined with DIO or not, alters the expression of critical genes involved in energy regulation imbalance in the hypothalamus, which warrants caution and more research, because long-term usage might be hazardous.

Oral solution of fructose promotes SREBP-1c high-expression in the hypothalamus of Wistar rats.

Objective: We evaluate whether the consumption of fructose for 8 weeks affects enzymes and transcription factors of the lipogenic and inflammatory pathways in the hypothalamus of Wistar rats. Methods: At 30 days, the animals were divided into groups: Control (C) and Fructose (F) and maintained with free access to feed and filtered water (C) or aqueous solution of purified fructose at 20% (F). RT-PCR and Western blotting were performed for the target genes and proteins. Results: In F group, results showed a lower feed intake, an increase in glycemia (146.20 ± 6.09 vs. 102.32 ± 4.58; n: 9) and triacylglycerol (F: 191.65 ± 13.51 vs. C: 131.69 ± 6.49; n: 9) and there was no difference in water and energy consumption. We identified a higher content of acetyl-CoA carboxylase (ACC) (F: 133.93 ± 5.58 vs. C: 100 ± 0.0; n: 9-10) and NFκB (F: 125.5 ± 8.85 vs. C: 100 ± 0; n: 14) in group F, whereas fatty acid synthase (FAS) was lower (F: 85.90 ± 4.81 vs. C: 100 ± 0.0; n: 4-6). SREBP-1c gene expression was higher in F vs. C group (F: 4.08 ± 0.44 vs. C: 1.13 ± 0.15; n: 5-6), although we did not found difference between groups in the gene expression for ACC, SREBP-2, and NFκB. Discussion: Dietary fructose can change important lipogenic and inflammatory factors in the hypothalamus of rats and it leads to regulation of transcription factors before changes in body mass are evident.

High-monosaccharide intake inhibits anorexigenic hypothalamic insulin response in male rats.

OBJECTIVE: The aim of this research is to evaluate if intake of 20% fructose solution is able to change the anorexigenic hypothalamic insulin action. METHODS: Thirty day-old male Wistar rats were randomly assigned to one of the following groups: standard chow and water for the rats (Control group, C) and standard chow and 20% fructose solution for the rats (Fructose group, F).These treatments lasted 8 weeks. Three-month-old rats from group C and F received insulin or saline intracerebroventricular injections for evaluation of 24 h food intake, phosphorylated forms of the IR (p-IR) and Akt (p-Akt) proteins and quantified hypothalamic insulin receptor (IR) and insulin receptor substrate 1 (IRS-1) proteins. RESULTS: Insulin injection was able to decrease food intake in group C compared to 0.9% saline. However, insulin infusion failed to inhibit 24 h food intake in group F compared to 0.9% saline. The hypothalamic content of the IRS-1 was 37% higher in group F as well as p-Akt protein was significant higher vs. group C. CONCLUSION: We concluded that the 20% fructose solution compromised insulin signaling considering that it inhibited the anorexigenic hypothalamic response to acute injection of this hormone and increase of IRS-1 and p-Akt content.

Effects of fructose consumption on food intake and biochemical and body parameters in Wistar rats. / Efeitos do consumo de frutose sobre ingestão alimentar, parâmetros bioquímicos e corporais em ratos Wistar.

INTRODUTION AND OBJECTIVE: Increased fructose consumption is associated with various metabolic changes that favor the onset of obesity and related comorbidities. The objective of this study was to assess the effects of chronic fructose consumption on body weight and adipose tissue, as well as on serum glucose and triglyceride levels. METHODS: Thirty-day-old Wistar rats were divided into two groups: fructose (F) and control (C), which had free access to commercial chow and either water or a 20% fructose solution. Body mass was measured weekly and food consumption at 30, 60 and 90 days. At 90 days, the animals were killed by decapitation and fat deposits (mesenteric, epididymal and retroperitoneal) were removed and blood collected for measurement of glucose and triglyceride levels. RESULTS: There was no significant difference in body weight gain, but the percentage of body fat was higher in group F. This group also consumed less feed at 60 and 90 days and had higher consumption of fructose solution than water in group C at 30 and 60 days. This meant higher calorie intake in group F and lower feed efficiency. Retroperitoneal and epididymal fat deposits and triglycerides were higher in group F than in group C. CONCLUSION: Consumption of fructose solution for eight weeks, while not directly reflected in body weight gain, did increase abdominal fat in group F compared to group C, as well as changing triglyceride levels. These two factors increase risk of cardiovascular disease.

Trans and interesterified fat and palm oil during the pregnancy and lactation period inhibit the central anorexigenic action of insulin in adult male rat offspring.

Palm oil and interesterified fat have been used to replace partially hydrogenated fats, rich in trans isomers, in processed foods. This study investigated whether the maternal consumption of normolipidic diets containing these lipids affects the insulin receptor and Akt/protein kinase B (PKB) contents in the hypothalamus and the hypophagic effect of centrally administered insulin in 3-month-old male offspring. At 90 days, the intracerebroventricular injection of insulin decreased 24-h feeding in control rats but not in the palm, interesterified or trans groups. The palm group exhibited increases in the insulin receptor content of 64 and 69 % compared to the control and trans groups, respectively. However, the quantifications of PKB did not differ significantly across groups. We conclude that the intake of trans fatty acid substitutes during the early perinatal period affects food intake regulation in response to centrally administered insulin in the young adult offspring; however, the underlying mechanisms remain unclear.

Ingestão de gordura trans na gestação e lactação inibe o efeito anorexígeno central da insulina e da serotonina na prole adulta / Trans fat intake during preegnancy and lactation inhibits the central anorexigenic effect in insulin and serotonin in the adult offspring

Os ácidos graxos trans (AGT) estão presentes no sangue e leite maternos em quantidades proporcionais à ingestão materna e são incorporados em diversos tecidos do organismo fetal e do neonato. No presente trabalho avaliamos se a ingestão materna de ácidos graxos trans na gestação e lactação afeta, nos filhotes machos adultos, a composição de ácidos graxos (AG) cerebrais, a sensibilidade à ação anorexígena central da insulina e serotonina e o teor hipotalâmico de proteínas que participam destes sistemas de homeostase energética. Ratas Wistar foram distribuídas em dois grupos, segundo a dieta ofertada durante toda a gestação e lactação: grupo Controle, que recebeu dieta à base de óleo de soja (8 por cento) como fonte de gordura e grupo Trans, que recebeu dieta à base de gordura vegetal hidrogenada (7 por cento) adicionada de 1 por cento de óleo de soja. Do desmame, realizado no 21 o dia da lactação, até os 3 meses de vida, a prole de machos controles foi mantida com a dieta controle (grupo Controle, C) enquanto a prole de machos trans foi distribuída em dois grupos: Trans-Controle (TC), o qual passou a receber dieta controle e grupo Trans (T) que permaneceu recebendo dieta trans. Aos 90 dias de vida avaliamos a ingestão alimentar de 24 horas, massa corporal, teor de proteína e gordura em carcaça, concentrações séricas de glicose e insulina e a ingestão alimentar em resposta à infusão intracerebroventricular (i.c.v.) de insulina (10 mU) ou serotonina (200 mg). Estabelecemos o perfil de AG dos lipídios totais do cérebro e hipotálamo e dos fosfolipídios do hipotálamo em animais de 21 e 90 dias. Quantificamos por "immunoblotting" o teor hipotalâmico do receptor de insulina (IR) e do substrato 1 do receptor de insulina (IRS-l) e também o teor dos receptores serotonérgicos lB (5HTIB) e 2C (5-HT2C) e do transportador de serotonina (5-HTT). Não observamos diferenças significantes na ingestão alimentar, massa corporal, teor de proteína e gordura em carcaça e insulinemia, entretanto verificamos concentração sérica elevada de glicose nos animais do grupo Trans-Controle. Não detectamos AGT no cérebro e hipotálamo do grupo Controle, havendo baixa...

Conseqüências do consumo materno de álcool durante a lactação sobre a distribuição de ácidos graxos nos fosfolipídios do cérebro de filhotes / Consequences of maternal consumption of alcohol during lactation in content of fatty acids in phospholipids of the brain pups

Tem sido demonstrado que a ingestão materna de álcool na lactação compromete o desenvolvimento do cérebro do neonato e que o álcool promove alterações nos lipídios de membranas, especialmente na composição de ácidos graxos (AG) dos fosfolipídios (PL). Neste trabalho analisamos a distribuição dos AG dos PL do cérebro de filhotes de mães alcoolizadas na lactação. O grupo álcool (AL) recebeu solução de etanol a 20 por cento e dieta ad libitum, o controle (C) recebeu dieta e água ad libitum e o pair-fed (PF) recebeu a mesma quantidade de dieta consumida pelo grupo AL e água ad libitum. Os resultados mostraram que o consumo de álcool na lactação promoveu no leite materno redução significativa no conteúdo do C14:0 e C22:6 e aumento do C18:0; C16:1 e C:18:1 em comparação aos C. As crias do grupo AL apresentaram menor ganho de peso e conteúdo do C20:3 e redução do C20:4, além de níveis indetectáveis do C22:6 nos PL do cérebro, comparando aos C. Com relação aos AG da fosfatidilcolina (PC) e fosfatidiletanolamina (PE) do cérebro de filhotes alcoolizados não observou-se diferenças significativas no conteúdo dos saturados, monoinsaturados e poliinsaturados totais, porém ao analisar-se os AG das séries n-6 e n-3, verificou-se um aumento significativo no conteúdo do C18:3 da PC comparado aos C, sem que detectássemos os seus metabólitos. Estes resultados indicam que o consumo materno de álcool nos 12 primeiros dias da lactação altera o conteúdo de AG do leite materno e compromete o desenvolvimento normal das crias além de promover importantes modificações no conteúdo de AG dos PL do cérebro. Tais alterações poderiam acarretar prejuízos nas funções cerebrais.