Ovariectomy modifies lipid metabolism of retroperitoneal white fat in rats: a proteomic approach.

Menopause is often accompanied by visceral obesity. With the aim of exploring the consequences of ovarian failure on visceral fat, we evaluated the effects of ovariectomy and estrogen replacement on the proteome/phosphoproteome and on the fatty acid profile of the retroperitoneal adipose depot (RAT) of rats. Eighteen 3-mo-old female Wistar rats were either ovariectomized or sham operated and fed with standard chow for 3 mo. A subgroup of ovariectomized rats received estradiol replacement. RAT samples were analyzed with data-independent acquisitions LC-MS/MS, and pathway analysis was performed with the differentially expressed/phosphorylated proteins. RAT lipid profile was analyzed by gas chromatography. Ovariectomy induced high adiposity and insulin resistance and promoted alterations in protein expression and phosphorylation. Pathway analysis showed that five pathways were significantly affected by ovariectomy, namely, metabolism of lipids (including fatty acid metabolism and mitochondrial fatty acid ß-oxidation), fatty acyl-CoA biosynthesis, innate immune system (including neutrophil degranulation), metabolism of vitamins and cofactors, and integration of energy metabolism (including ChREBP activates metabolic gene expression). Lipid profile analysis showed increased palmitic and palmitoleic acid content. The analysis of the data indicated that ovariectomy favored lipogenesis whereas it impaired fatty acid oxidation and induced a proinflammatory state in the visceral adipose tissue. These effects are consistent with the findings of high adiposity, hyperleptinemia, and impaired insulin sensitivity. The observed alterations were partially attenuated by estradiol replacement. The data point to a role of disrupted lipid metabolism in adipose tissue in the genesis of obesity after menopause.

High-fat diet intake induces depressive-like behavior in ovariectomized rats.

This study tested the effects of ovariectomy, allied or not to high-fat feeding and estradiol replacement, on hormonal, metabolic and behavioral parameters, to explore the connection of obesity and depression after menopause. Wistar rats were either ovariectomized or sham-operated and fed with either standard chow or lard-enriched diet for twelve weeks. Sub-groups of ovariectomized rats received estradiol replacement. Depressive-like behaviors were assessed by the forced swim test and locomotor activity was assessed by the elevated plus maze test. Ovariectomy alone increased body weight gain and feed efficiency and induced hyperleptinemia and glucose intolerance while it increased caloric intake and body adiposity only marginally. High-fat intake alone induced obesity and, in combination with ovariectomy, accentuated the ovariectomy-induced alterations. Estradiol replacement attenuated the hormonal alterations only in chow-fed rats. Ovariectomy combined with high-fat intake induced depressive-like behaviors, which were marginally attenuated by estradiol. Depressive-like behaviors were associated with metabolic and body composition parameters and with estrogen status. The data indicate that the vulnerability to develop depression after menopause is influenced by high-fat intake. It is suggested that weight management is a crucial issue in postmenopausal women, probably having a beneficial role in preventing the appearance of mental health problems.

Effect of fish oil intake on glucose levels in rat prefrontal cortex, as measured by microdialysis.

BACKGROUND: Brain glucose sensing may contribute to energy homeostasis control. The prefrontal cortex (PFC) participates in the hedonic component of feeding control. As high-fat diets may disrupt energy homeostasis, we evaluated in male Wistar rats whether intake of high-fat fish-oil diet modified cortical glucose extracellular levels and the feeding induced by intracerebroventricular glucose or PFC glucoprivation. METHODS: Glucose levels in PFC microdialysates were measured before and after a 30-min meal. Food intake was measured in animals receiving intracerebroventricular glucose followed, 30-min. later, by 2-deoxy-D-glucose injected into the PFC. RESULTS: The fish-oil group showed normal body weight and serum insulin while fat pads weight and glucose levels were increased. Baseline PFC glucose and 30-min. carbohydrates intake were similar between the groups. Feeding-induced PFC glucose levels increased earlier and more pronouncedly in fish-oil than in control rats. Intracerebroventricular glucose inhibited feeding consistently in the control but not in the fish-oil group. Local PFC glucoprivation with 2-DG attenuated glucose-induced hypophagia. CONCLUSIONS: The present experiments have shown that, following food intake, more glucose reached the prefrontal cortex of the rats fed the high-fat fish-oil diet than of the rats fed the control diet. However, when administered directly into the lateral cerebral ventricle, glucose was able to consistently inhibit feeding only in the control rats. The findings indicate that, an impairment of glucose transport into the brain does not contribute to the disturbances induced by the high-fat fish-oil feeding.

High-fat diets rich in soy or fish oil distinctly alter hypothalamic insulin signaling in rats.

Hypothalamic insulin inhibits food intake, preventing obesity. High-fat feeding with polyunsaturated fats may be obesogenic, but their effect on insulin action has not been elucidated. The present study evaluated insulin hypophagia and hypothalamic signaling after central injection in rats fed either control diet (15% energy from fat) or high-fat diets (50% energy from fat) enriched with either soy or fish oil. Soy rats had increased fat pad weight and serum leptin with normal body weight, serum lipid profile and peripheral insulin sensitivity. Fish rats had decreased body and fat pad weight, low leptin and corticosterone levels, and improved serum lipid profile. A 20-mU dose of intracerebroventricular (ICV) insulin inhibited food intake in control and fish groups, but failed to do so in the soy group. Hypothalamic protein levels of IR, IRS-1, IRS-2, Akt, mTOR, p70S6K and AMPK were similar among groups. ICV insulin stimulated IR tyrosine phosphorylation in control (68%), soy (36%) and fish (34%) groups. Tyrosine phosphorylation of the pp185 band was significantly stimulated in control (78%) and soy (53%) rats, but not in fish rats. IRS-1 phosphorylation was stimulated only in control rats (94%). Akt serine phosphorylation was significantly stimulated only in control (90%) and fish (78%) rats. The results showed that, rather than the energy density, the fat type was a relevant aspect of high-fat feeding, since blockade of hypothalamic insulin signal transmission and insulin hypophagia was promoted only by the high-fat soy diet, while they were preserved in the rats fed with the high-fat fish diet.

Alterations in downstream mediators involved in central control of eating behavior in obese adolescents submitted to a multidisciplinary therapy.

OBJECTIVE: The aim of this study was to verify the effects of a multidisciplinary therapy (24 weeks) on neurohormonal control of food intake, specifically in orexigenic (total ghrelin, agouti-related protein [AgRP], neuropeptide Y [NPY], and melanin-concentrating hormone) and anorexigenic factors (leptin, insulin, and alpha-melanocyte stimulating hormone [α-MSH]), in obese adolescents. METHODS: A total of 88 adolescents (38 boys and 50 girls), including 62 obese and 26 normal-weight, aged 15-19 years were recruited. Obese adolescents were submitted to a 24-week multidisciplinary therapy. AgRP, NPY, melanin-concentrating hormone, leptin, insulin, glucose, α-MSH, total ghrelin, and food intake were measured at three stages (at baseline, after 12 weeks, and after 24 weeks). RESULTS: At baseline, obese adolescents showed hyperleptinemia (circulating leptin levels, which were, in boys and girls, 40 and 35 times higher than in normal-weight subjects, respectively). After 24 weeks, these values decreased in all obese patients. Our results showed no differences in ghrelin levels between obese and normal-weight adolescents, in both genders. However, obese boys reduced their plasma ghrelin concentration after 24 weeks of therapy (p < .05). The multidisciplinary therapy decreased NPY and AgRP values and increased α-MSH; simultaneously with these changes there was a decrease in total food intake after 24 weeks of therapy. CONCLUSIONS: We can conclude that the multidisciplinary therapy was efficient to modulate neurohormonal control of food intake in obese adolescents.

Soybean and fish oil mixture increases IL-10, protects against DNA damage and decreases colonic inflammation in rats with dextran sulfate sodium (DSS) colitis.

It was investigated whether dietary polyunsaturated fatty acids (PUFA) could influence colonic injury, tissue DNA damage, cytokines and myeloperoxidase activity (MPO) and plasma corticosterone in DSS-induced colitis rats. Male weaning Wistar rats were fed for 47 days with an AIN-93 diet with control (C), fish (F) or a mixture of fish and soybean oil (SF). The colitis was induced from day 36 until day 42 by 3% DSS in drinking water. On day 48, blood samples were collected for corticosterone determination. The distal colon was excised for histological analysis and to quantify the cytokine (IL-4, IL-10 and INF-gamma), MPO and DNA damage. The disease activity index (DAI) was recorded daily during colitis induction. The DAI, MPO, histological analyses showed decreases only in the SF group compared with the C group. IL-10 was increased and DNA damage was reduced in the groups F and SF, and an inverse correlation between these variables was found. There were no differences in corticosterone, IFN-gamma and IL-4 levels. Soybean and fish oil mixture may be effective in improving colonic injury and DNA damage, and it could be an important complementary therapy in UC to reduce the use of anti-inflammatory drugs and prevent colorectal cancer.

Long-term consumption of fish oil-enriched diet impairs serotonin hypophagia in rats.

Hypothalamic serotonin inhibits food intake and stimulates energy expenditure. High-fat feeding is obesogenic, but the role of polyunsaturated fats is not well understood. This study examined the influence of different high-PUFA diets on serotonin-induced hypophagia, hypothalamic serotonin turnover, and hypothalamic protein levels of serotonin transporter (ST), and SR-1B and SR-2C receptors. Male Wistar rats received for 9 weeks from weaning a diet high in either soy oil or fish oil or low fat (control diet). Throughout 9 weeks, daily intake of fat diets decreased such that energy intake was similar to that of the control diet. However, the fish group developed heavier retroperitoneal and epididymal fat depots. After 12 h of either 200 or 300 µg intracerebroventricular serotonin, food intake was significantly inhibited in control group (21-25%) and soy group (37-39%) but not in the fish group. Serotonin turnover was significantly lower in the fish group than in both the control group (-13%) and the soy group (-18%). SR-2C levels of fish group were lower than those of control group (50%, P = 0.02) and soy group (37%, P = 0.09). ST levels tended to decrease in the fish group in comparison to the control group (16%, P = 0.339) and the soy group (21%, P = 0.161). Thus, unlike the soy-oil diet, the fish-oil diet decreased hypothalamic serotonin turnover and SR-2C levels and abolished serotonin-induced hypophagia. Fish-diet rats were potentially hypophagic, suggesting that, at least up to this point in its course, the serotonergic impairment was either compensated by other factors or not of a sufficient extent to affect feeding. That fat pad weight increased in the absence of hyperphagia indicates that energy expenditure was affected by the serotonergic hypofunction.

Nutritional recovery with rice bran did not modify energy balance and leptin and insulin levels / Recuperação nutricional com farelo de arroz não modificou o balanço energético e os níveis de leptina e insulina

OBJECTIVE: To investigate the effect of nutritional recovery with rice bran on energy balance, leptin and insulin levels. METHODS: Weaned Wistar rats were fed on a 17 percent (Control - C) or 0.5 percent (Aproteic - A) protein diet for 12d. After this, rats were kept on a C diet (C) or recovered with control (Recovered Control - RC) or control plus recovered rice bran diet (Recovered Rice Bran - RRB). RESULTS: Despite the increased food intake, group A exhibited lower carcass fat associated to low serum leptin. RRB and RC groups showed lower carcass weight and energy intake and expenditure. Energy expenditure was positively associated with food intake and carcass weight. Negative correlations between HOMA-IR and energy expenditure and energy intake were observed. CONCLUSION: Nutritional recovery with rice bran did not modify energy balance, leptin and insulin levels.

OBJETIVO: Investigar o efeito da recuperação nutricional com farelo de arroz sobre o balanço energético e níveis de leptina e insulina. MÉTODOS: Ratos Wistar recém-desmamados foram alimentados com 17 por cento (Controle - C) ou 0,5 por cento (Aproteico - A) de proteína (caseína) durante 12 dias. Em seguida, ratos permaneceram com dieta controle (C) ou foram recuperados com controle (Recuperados Controle - RC) ou controle mais 5 por cento de farelo de arroz (Recuperados com Farelo de Arroz - RFA) durante 21 dias. RESULTADOS: Apesar de a ingestão alimentar ter sido maior em A, a gordura na carcaça foi reduzida, sendo associada com menor nível de leptina. Os grupos RFA e RC tiveram redução no peso da carcaça, no gasto e ingestão de energia. O gasto energético foi correlacionado com a ingestão de alimentos e o peso da carcaça fresco. Foi observada correlação negativa entre HOMA-IR com gasto energético e com ingestão de energia. CONCLUSÃO: A recuperação nutricional com farelo de arroz não modificou o balanço energético, nem os níveis de leptina e insulina.

Prolonged consumption of soy or fish-oil-enriched diets differentially affects the pattern of hypothalamic neuronal activation induced by refeeding in rats.

We used c-Fos immunoreactivity to estimate neuronal activation in hypothalamic feeding-regulatory areas of 3-month-old rats fed control or oil-enriched diets (soy or fish) since weaning. While no diet effect was observed in c-Fos immunoreactivity of 24-h fasted animals, the acute response to refeeding was modified by both hyperlipidic diets but with different patterns. Upon refeeding, control-diet rats had significantly increased c-Fos immunoreactivity only in the paraventricular hypothalamic nucleus (PVH, 142%). In soy-diet rats, refeeding with the soy diet increased c-Fos immunoreactivity in dorsomedial hypothalamic nucleus (DMH, 271%) and lateral hypothalamic area (LH, 303%). Refeeding fish-diet rats with the fish diet increased c-Fos immunoreactivity in PVH (161%), DMH (177%), VMH (81%), and ARC (127%). Compared to the fish-diet, c-Fos immunoreactivity was increased in LH by the soy-diet while it was decreased in ventromedial hypothalamic nucleus (VMH) and arcuate hypothalamic nucleus (ARC). Based on the known roles of the activated nuclei, it is suggested that, unlike the fish-diet, the soy-diet induced a potentially obesogenic profile, with high LH and low VMH/PVH activation after refeeding.

Diets rich in polyunsaturated fatty acids: effect on hepatic metabolism in rats.

OBJECTIVE: We investigated the effect of diets rich in omega-6 and omega-3 fatty acids on hepatic metabolism. METHODS: Male Wistar rats, just weaned, were fed ad libitum for 8 wk with one of the following diets: rat chow (C), rat chow containing 15% (w/w) soybean oil (S), rat chow containing 15% (w/w) fish oil (F), and rat chow containing 15% soy bean and fish oil (SF; 5:1, w/w). Casein was added to the fatty diets to achieve the same content of protein (20%) as the control chow. The rats were killed by decapitation, and the hepatic tissue was removed and weighed. Tissue lipid, glycogen, and protein content, in vivo lipogenesis rate, and adenosine triphosphate citrate lyase and malic enzyme activities were evaluated. Plasma total lipids, triacylglycerol, and cholesterol concentrations were assessed. RESULTS: Body weight gain was higher in F and SF than in C and S rats. Liver weight, lipid content, and lipogenesis rate increased in F and SF rats, although adenosine triphosphate citrate lyase activity decreased. Glycogen concentration decreased in S, F, and SF rats compared with C rats. Plasma total lipids and triacylglycerol concentrations were lower in F and SF than in C rats. Total and high-density lipoprotein cholesterol (HDL-C) plasma levels decreased in F rats, with maintenance of the total:HDL-C ratio. In SF rats, an increase in HDL-C led to a lower total:HDL-C ratio. CONCLUSIONS: These results indicated that an enrichment of the diet with omega-3 polyunsaturated fatty acids produces hypolipidemia but may cause changes in liver metabolism that favor lipid deposition. They also suggested that the addition of a small amount of eicosapentaenoic and docosahexaenoic polyunsaturated fatty acids to an omega-6-rich diet further improve the circulating lipid profile, in comparison with an omega-3-rich diet, but it does not prevent excess liver lipid accumulation.

Obesidade: subsídios para o desenvolvimento de atividades motoras / Obesity: basis for the development of motor activities

Pode a criança obesa tornar-se um adulto obeso? Nao existem evidências convincentes de que uma criança obesa venha tornar-se um adulto obeso; entretanto, muitos autores têm sugerido que dois terços das crianças obesas permanecem obesas na vida adulta. Estudos sobre o desenvolvimento da celularidade adiposa domonstram que existe um período crítico na infância que determina os riscos para a obesidade futura. O presente trabalho tem como objetivo apresentar questoes relevantes no que diz respeito à intervençao precoce nos padroes de obesidade, principalmente no período da infância e adolescência. Desta forma, serao considerados conteúdos voltados à origem, características, conseqüências, avaliaçao da atividade motora, composiçao corporal e intervençao multidisciplinar.