Fish oil supplementation during pregnancy decreases liver endocannabinoid system and lipogenic markers in newborn rats exposed to maternal high-fat diet.

PURPOSE: Maternal high-fat diet (HF) programs obesity, metabolic dysfunction-associated steatotic liver disease (MASLD), hypertriglyceridemia, and hyperglycemia associated with increased endocannabinoid system (ECS) in the liver of adult male rat offspring. We hypothesized that maternal HF would induce sex specific ECS changes in the liver of newborn rats, prior to obesity onset, and maternal fish oil (FO) supplementation would reprogram the ECS and lipid metabolism markers preventing liver triglycerides (TG) accumulation. METHODS: Female rats received a control (CT) (10.9% fat) or HF (28.7% fat) diet 8 weeks prior to mating and during pregnancy. A subgroup of HF dams received 3% FO supplementation in the HF diet (35.4% fat) during pregnancy (HFFO). Serum hormones and liver TG, ECS, lipid metabolism, oxidative stress and autophagy markers were assessed in male and female newborn offspring. RESULTS: Maternal HF diet increased liver cannabinoid receptor 1 (CB1) in males and decreased CB2 in females, with no effect on liver TG. Maternal FO supplementation reduced liver CB1 regardless of the offspring sex, but reduced TG liver content only in females. FO reduced the liver content of the endocannabinoid anandamide in males, and the content of 2-arachidonoylglycerol in both sexes. Maternal HF increased lipogenic and decreased lipid oxidation markers, and FO induced the opposite regulation in the liver of offspring. CONCLUSION: Prenatal HF and FO differentially modulate liver ECS in the offspring before obesity and MASLD development. These results suggest that maternal nutrition at critical stages of development can modulate the offspring's ECS, predisposing or preventing the onset of metabolic diseases.

Estrogen normalizes maternal HFD-induced vascular dysfunction in offspring by regulating ATR.

Previous studies have shown that female offspring are resistant to fetal high-fat diet (HFD)-induced programming of heightened vascular contraction; however, the underlying mechanisms remain unclear. The present study tested the hypothesis that estrogen plays a key role in protecting females from fetal programming of increased vascular contraction induced by maternal HFD exposure. Pregnant rats were fed a normal diet (ND) or HFD (60% kcal from fat). Ovariectomy (OVX) and 17ß-estradiol (E2) replacement were performed on 8-week-old female offspring. Aortas were isolated from adult female offspring. Maternal HFD exposure increased angiotensin II (Ang II)-induced contractions of the aorta in adult OVX offspring, which was abrogated by E2 replacement. The AT1 receptor (AT1R) antagonist losartan (10 µM), but not the AT2 receptor (AT2R) antagonist PD123319 (10 µM), completely blocked Ang II-induced contractions in both ND and HFD offspring. In addition, HFD exposure caused a decrease in endothelium-dependent relaxations induced by acetylcholine (ACh) in adult OVX but not OVX-E2 offspring. However, it had no effect on sodium nitroprusside (SNP)-induced endothelium-independent aorta relaxation in any of the six groups. Maternal HFD feeding increased AT1R, but not AT2R, leading to an increased AT1R/AT2R ratio in HFD-exposed OVX offspring, associated with selective decreases in DNA methylation at the AT1aR promoter, which was ameliorated by E2 replacement. Our results indicated that estrogen play a key role in sex differences of maternal HFD-induced vascular dysfunction and development of hypertensive phenotype in adulthood by differently regulating vascular AT1R and AT2R gene expression through a DNA methylation mechanism.

Maternal High-Fat Feeding Affects the Liver and Thymus Metabolic Axis in the Offspring and Some Effects Are Attenuated by Maternal Diet Normalization in a Minipig Model.

Maternal high-fat diet (HFD) affects metabolic and immune development. We aimed to characterize the effects of maternal HFD, and the subsequent diet-normalization of the mothers during a second pregnancy, on the liver and thymus metabolism in their offspring, in minipigs. Offspring born to high-fat (HFD) and normal diet (ND) fed mothers were studied at week 1 and months 1, 6, 12 of life. Liver and thymus glucose uptake (GU) was measured with positron emission tomography during hyperinsulinemic-isoglycemia. Histological analyses were performed to quantify liver steatosis, inflammation, and hepatic hematopoietic niches (HHN), and thymocyte size and density in a subset. The protocol was repeated after maternal-diet-normalization in the HFD group. At one week, HFDoff were characterized by hyperglycemia, hyperinsulinemia, severe insulin resistance (IR), and high liver and thymus GU, associating with thymocyte size and density, with elevated weight-gain, liver IR, and steatosis in the first 6 months of life. Maternal diet normalization reversed thymus and liver hypermetabolism, and increased HHN at one week. It also normalized systemic insulin-sensitivity and liver fat content at all ages. Instead, weight-gain excess, hyperglycemia, and hepatic IR were still observed at 1 month, i.e., end-lactation. We conclude that intra-uterine HFD exposure leads to time-changing metabolic and immune-correlated abnormalities. Maternal diet-normalization reversed most of the effects in the offspring.

Maternal High-Fat Diet Promotes Abdominal Aortic Aneurysm Expansion in Adult Offspring by Epigenetic Regulation of IRF8-Mediated Osteoclast-like Macrophage Differentiation.

Maternal high-fat diet (HFD) modulates vascular remodeling in adult offspring. Here, we investigated the impact of maternal HFD on abdominal aortic aneurysm (AAA) development. Female wild-type mice were fed an HFD or normal diet (ND). AAA was induced in eight-week-old pups using calcium chloride. Male offspring of HFD-fed dams (O-HFD) showed a significant enlargement in AAA compared with the offspring of ND-fed dams (O-ND). Positive-staining cells for tartrate-resistant acid phosphate (TRAP) and matrix metalloproteinase (MMP) activity were significantly increased in O-HFD. The pharmacological inhibition of osteoclastogenesis abolished the exaggerated AAA development in O-HFD. The in vitro tumor necrosis factor-α-induced osteoclast-like differentiation of bone marrow-derived macrophages showed a higher number of TRAP-positive cells and osteoclast-specific gene expressions in O-HFD. Consistent with an increased expression of nuclear factor of activated T cells 1 (NFATc1) in O-HFD, the nuclear protein expression of interferon regulatory factor 8 (IRF8), a transcriptional repressor, were much lower, with significantly increased H3K27me3 marks at the promoter region. The enhancer of zeste homolog 2 inhibitor treatment restored IRF8 expression, resulting in no difference in NFATc1 and TRAP expressions between the two groups. Our findings demonstrate that maternal HFD augments AAA expansion, accompanied by exaggerated osteoclast-like macrophage accumulation, suggesting the possibility of macrophage skewing via epigenetic reprogramming.

Açaí (Euterpe oleracea Martius) supplementation improves oxidative stress biomarkers in liver tissue of dams fed a high-fat diet and increases antioxidant enzymes' gene expression in offspring.

Lipids excess from an uterine environment can increase free radicals production of and thus induce oxidative status imbalance, a key factor for progression of non-alcoholic fatty liver disease (NAFLD) in offspring. Food antioxidant components in maternal diet may play an important role in preventing offspring metabolic disorders. The objective of the study was to evaluate the effects of açaí pulp supplementation on maternal high-fat diet, by assessing activity and expression of antioxidant enzymes and biomarkers of oxidative stress in the liver. Female Fisher rats were divided into four groups and fed a control diet (C), a high-fat diet (HF), a control diet supplemented with açaí (CA) and a high-fat diet supplemented with açaí (HFA) before mating, during gestation and lactation. The effects of açaí supplementation on oxidative stress biomarkers and antioxidant enzymes expression were evaluated in dams and male offspring after weaning. HFA diet increased body weight in dams, however reduced absolute and relative liver weight. There was a reduction in liver biomarkers of oxidative stress, malondialdehyde and carbonyl protein, as well as in catalase, glutathione peroxidase and superoxide dismutase activity. In offspring, HFA diet reduced liver weight and increased Gpx1, Gpx4 and Sod1 mRNA expression. These results suggest that açaí is able to restore redox status, preventing oxidative damage in dams by a direct mechanism and to promote beneficial effects on expression of antioxidant defences related genes in offspring.

Estrogen normalizes maternal HFD-induced cardiac hypertrophy in offspring by regulating AT2R.

Our previous study has demonstrated maternal high-fat diet (HFD) caused sex-dependent cardiac hypertrophy in adult male, but not female offspring. The present study tested the hypothesis that estrogen normalizes maternal HFD-induced cardiac hypertrophy by regulating angiotensin II receptor (ATR) expression in adult female offspring. Pregnant rats were divided into the normal diet (ND) and HFD (60% kcal fat) groups. Ovariectomy (OVX) and 17ß-estradiol (E2) replacement were performed on 8-week-old female offspring. Maternal HFD had no effect on left ventricular (LV) wall thickness, cardiac function and molecular markers of cardiac hypertrophy function in sham groups. However, maternal HFD caused cardiac hypertrophy of offspring in OVX groups, which was abrogated by E2 replacement. In addition, maternal HFD had no effect on ERα and ERß in sham groups. In contrast, HFD significantly decreased ERα, but not ERß in OVX groups. In sham groups, there was no difference in the cardiac ATR type 1 (AT1R) and ATR type 2 (AT2R) between ND and HFD offspring. HFD significantly increased AT2R, but not AT1R in OVX groups. Furthermore, maternal HFD resulted in decreased glucocorticoid receptors (GRs) binding to the glucocorticoid response elements at the AT2R promoter, which was due to decreased GRs in hearts from OVX offspring. These HFD-induced changes in OVX groups were abrogated by E2 replacement. These results support a key role of estrogen in the sex difference of maternal HFD-induced cardiac hypertrophy in offspring, and suggest that estrogen protects female offspring from cardiac hypertrophy in adulthood by regulating AT2R.

Amylin receptor insensitivity impairs hypothalamic POMC neuron differentiation in the male offspring of maternal high-fat diet-fed mice.

OBJECTIVE: Amylin was found to regulate glucose and lipid metabolism by acting on the arcuate nucleus of the hypothalamus (ARC). Maternal high-fat diet (HFD) induces sex-specific metabolic diseases mediated by the ARC in offspring. This study was performed to explore 1) the effect of maternal HFD-induced alterations in amylin on the differentiation of hypothalamic neurons and metabolic disorders in male offspring and 2) the specific molecular mechanism underlying the regulation of amylin and its receptor in response to maternal HFD. METHODS: Maternal HFD and gestational hyper-amylin mice models were established to explore the role of hypothalamic amylin and receptor activity-modifying protein 3 (Ramp3) in regulating offspring metabolism. RNA pull-down, mass spectrometry, RNA immunoprecipitation, and RNA decay assays were performed to investigate the mechanism underlying the influence of maternal HFD on Ramp3 deficiency in the fetal hypothalamus. RESULTS: Male offspring with maternal HFD grew heavier and developed metabolic disorders, whereas female offspring with maternal HFD showed a slight increase in body weight and did not develop metabolic disorders compared to those exposed to maternal normal chow diet (NCD). Male offspring exposed to a maternal HFD had hyperamylinemia from birth until adulthood, which was inconsistent with offspring exposed to maternal NCD. Hyperamylinemia in the maternal HFD-exposed male offspring might be attributed to amylin accumulation following Ramp3 deficiency in the fetal hypothalamus. After Ramp3 knockdown in hypothalamic neural stem cells (htNSCs), amylin was found to fail to promote the differentiation of anorexigenic alpha-melanocyte-stimulating hormone-proopiomelanocortin (α-MSH-POMC) neurons but not orexigenic agouti-related protein-neuropeptide Y (AgRP-Npy) neurons. An investigation of the mechanism involved showed that IGF2BP1 could specifically bind to Ramp3 in htNSCs and maintain its mRNA stability. Downregulation of IGF2BP1 in htNSCs in the HFD group could decrease Ramp3 expression and lead to an impairment of α-MSH-POMC neuron differentiation. CONCLUSIONS: These findings suggest that gestational exposure to HFD decreases the expression of IGF2BP1 in the hypothalami of male offspring and destabilizes Ramp3 mRNA, which leads to amylin resistance. The subsequent impairment of POMC neuron differentiation induces sex-specific metabolic disorders in adulthood.

Microglial and peripheral immune priming is partially sexually dimorphic in adolescent mouse offspring exposed to maternal high-fat diet.

BACKGROUND: Maternal nutrition is critical for proper fetal development. While increased nutrient intake is essential during pregnancy, an excessive consumption of certain nutrients, like fat, can lead to long-lasting detrimental consequences on the offspring. Animal work investigating the consequences of maternal high-fat diet (mHFD) revealed in the offspring a maternal immune activation (MIA) phenotype associated with increased inflammatory signals. This inflammation was proposed as one of the mechanisms causing neuronal circuit dysfunction, notably in the hippocampus, by altering the brain-resident macrophages-microglia. However, the understanding of mechanisms linking inflammation and microglial activities to pathological brain development remains limited. We hypothesized that mHFD-induced inflammation could prime microglia by altering their specific gene expression signature, population density, and/or functions. METHODS: We used an integrative approach combining molecular (i.e., multiplex-ELISA, rt-qPCR) and cellular (i.e., histochemistry, electron microscopy) techniques to investigate the effects of mHFD (saturated and unsaturated fats) vs control diet on inflammatory priming, as well as microglial transcriptomic signature, density, distribution, morphology, and ultrastructure in mice. These analyses were performed on the mothers and/or their adolescent offspring at postnatal day 30. RESULTS: Our study revealed that mHFD results in MIA defined by increased circulating levels of interleukin (IL)-6 in the mothers. This phenotype was associated with an exacerbated inflammatory response to peripheral lipopolysaccharide in mHFD-exposed offspring of both sexes. Microglial morphology was also altered, and there were increased microglial interactions with astrocytes in the hippocampus CA1 of mHFD-exposed male offspring, as well as decreased microglia-associated extracellular space pockets in the same region of mHFD-exposed offspring of the two sexes. A decreased mRNA expression of the inflammatory-regulating cytokine Tgfb1 and microglial receptors Tmem119, Trem2, and Cx3cr1 was additionally measured in the hippocampus of mHFD-exposed offspring, especially in males. CONCLUSIONS: Here, we described how dietary habits during pregnancy and nurturing, particularly the consumption of an enriched fat diet, can influence peripheral immune priming in the offspring. We also found that microglia are affected in terms of gene expression signature, morphology, and interactions with the hippocampal parenchyma, in a partially sexually dimorphic manner, which may contribute to the adverse neurodevelopmental outcomes on the offspring.

Maternal high-fat diet exaggerates diet-induced insulin resistance in adult offspring by enhancing inflammasome activation through noncanonical pathway of caspase-11.

OBJECTIVE: Maternal high-fat diet (HFD) has been shown to promote the development of insulin resistance (IR) in adult offspring; however, the underlying mechanisms remain unclear. METHODS: Eight-week-old female wild-type mice (C57BL/6) were fed either an HFD or a normal diet (ND), one week prior to mating, and the diet was continued throughout gestation and lactation. Eight-week-old male offspring of both groups were fed an HFD for 8 weeks. RESULTS: Offspring of HFD-fed dams (O-HFD) exhibited significantly impaired insulin sensitivity compared with the offspring of ND-fed dams (O-ND). The adipocyte size of the eWAT increased significantly in O-HFD and was accompanied by abundant crown-like structures (CLSs), as well as a higher concentration of interleukin 1ß (IL-1ß) in the eWAT. Treatment with an inflammasome inhibitor, MCC950, completely abrogated the enhanced IR in O-HFD. However, ex vivo caspase-1 activity in eWAT revealed no difference between the two groups. In contrast, noncanonical inflammasome activation of caspase-11 was significantly augmented in O-HFD compared with O-ND, suggesting that membrane pore formation, but not cleavage of pro-IL-1ß by caspase-1, is augmented in O-HFD. To examine the membrane pore formation, we performed metabolic activation of bone marrow-derived macrophages (BMDMs). The percentage of pore formation assessed by ethidium bromide staining was significantly higher in BMDMs of O-HFD, accompanied by an enhanced active caspase-11 expression. Consistently, the concentration of IL-1ß in culture supernatants was significantly higher in the BMDMs from O-HFD than those from O-ND. CONCLUSIONS: These findings demonstrate that maternal HFD exaggerates diet-induced IR in adult offspring by enhancing noncanonical caspase-11-mediated inflammasome activation.

Blockade of angiotensin-converting enzyme or tumor necrosis factor-α reverses maternal high-fat diet-induced sensitization of angiotensin II hypertension in male rat offspring.

Maternal high-fat diet (HFD) is associated with metabolic syndrome and cardiovascular diseases in adult offspring. Our previous study demonstrated that maternal HFD enhances pressor responses to ANG II or a proinflammatory cytokine (PIC), which is associated with increased expression of brain renin-angiotensin system (RAS) components and PICs in adult offspring. The present study further investigated whether inhibition of angiotensin-converting enzyme (ACE) or tumor necrosis factor-α (TNF-α) blocks sensitization of ANG II hypertension in offspring of HFD dams. All offspring were bred from dams with normal fat diet (NFD) or HFD starting two weeks before mating and maintained until weaning of the offspring. Then the weaned offspring were treated with an ACE inhibitor (captopril) or a TNF-α inhibitor (pentoxifylline) in the drinking water through the end of testing with a slow-pressor dose of ANG II. RT-PCR analyses of the lamina terminalis and paraventricular nucleus revealed upregulation of mRNA expression of several RAS components and PICs in male offspring of HFD dams when compared with age-matched offspring of NFD dams. The enhanced gene expression was attenuated by blockade of either RAS or PICs. Likewise, ANG II administration produced an augmented pressor response in offspring of HFD dams. This was abolished by either ACE or TNF-α inhibitor. Taken together, this study provides mechanistic evidence and a therapeutic strategy that systemic inhibition of the RAS and PICs can block maternal HFD-induced sensitization of ANG II hypertension, which is associated with attenuation of brain RAS and PIC expression in offspring.

Effects of troxerutin on inflammatory cytokines and BDNF levels in male offspring of high-fat diet fed rats.

OBJECTIVE: In the present study, we aimed to examine the effect of troxerutin treatment on levels of brain-derived neurotrophic factor (BDNF), and tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6), as pro-inflammatory cytokines, in the blood and hippocampus of high-fat diet (HFD) fed dams and their male offspring. MATERIALS AND METHODS: Forty virgin female Wistar rats, 3 weeks old, were divided into two groups (n=20/per group) and fed control diet (CD), or HFD for 8 weeks. After mating, pregnant animals were assigned to four subgroups including: control (CD), control+troxerutin (CD+T), high-fat diet (HFD), and HFD+troxerutin (HFD+T) groups. HFD was continued during pregnancy and lactation. Troxerutin (150 mg/kg/day, P.O.) was administered during pregnancy in the CD+T and HFD+T groups. On postnatal day (PND) 21, male offspring were separated and fed a normal diet until PND 90. Inflammatory cytokines (TNF-α, and IL-6) and BDNF levels were measured in the serum and hippocampal samples using rat-specific enzyme-linked immunosorbent assay (ELISA) kits. RESULTS: Our findings showed a significant increase in the serum levels of TNF-α and IL-6, but a decrease in BDNF levels in the serum of HFD-fed dams in comparison with CD group, which was reversed by troxerutin. Moreover, troxerutin treatment, during pregnancy, significantly decreased TNF-α and IL-6 levels, but increased BDNF level in the serum and hippocampus of HFD+T offspring in comparison with HFD offspring. CONCLUSION: These results showed that troxerutin could prevent the harmful effects of maternal HFD on their offspring through inhibition of pro-inflammatory cytokines and elevation of BDNF levels.

Fish oil supplementation during adolescence attenuates metabolic programming of perinatal maternal high-fat diet in adult offspring.

Perinatal maternal high-fat diet (HFD) increases susceptibility to obesity and fatty liver diseases in adult offspring, which can be attenuated by the potent hypolipidaemic action of fish oil (FO), an n-3 PUFA source, during adult life. Previously, we described that adolescent HFD offspring showed resistance to FO hypolipidaemic effects, although FO promoted hepatic molecular changes suggestive of reduced lipid accumulation. Here, we investigated whether this FO intervention only during the adolescence period could affect offspring metabolism in adulthood. Then, female Wistar rats received isoenergetic, standard (STD: 9 % fat) or high-fat (HFD: 28·6 % fat) diet before mating, and throughout pregnancy and lactation. After weaning, male offspring received the standard diet; and from 25 to 45 d old they received oral administration of soyabean oil or FO. At 150 d old, serum and hepatic metabolic parameters were evaluated. Maternal HFD adult offspring showed increased body weight, visceral adiposity, hyperleptinaemia and decreased hepatic pSTAT3/STAT3 ratio, suggestive of hepatic leptin resistance. FO intake only during the adolescence period reduced visceral adiposity and serum leptin, regardless of maternal diet. Maternal HFD promoted dyslipidaemia and hepatic TAG accumulation, which was correlated with reduced hepatic carnitine palmitoyl transferase-1a content, suggesting lipid oxidation impairment. FO intake did not change serum lipids; however, it restored hepatic TAG content and hepatic markers of lipid oxidation to STD offspring levels. Therefore, we concluded that FO intake exclusively during adolescence programmed STD offspring and reprogrammed HFD offspring male rats to a healthier metabolic phenotype in adult life, reducing visceral adiposity, serum leptin and hepatic TAG content in offspring adulthood.

Perinatal maternal high-fat diet promotes alterations in hepatic lipid metabolism and resistance to the hypolipidemic effect of fish oil in adolescent rat offspring.

SCOPE: Maternal high-fat diet (HFD) promotes obesity and metabolic disturbances in offspring at weaning and adult life. We investigated metabolic consequences of maternal HFD in adolescent rat offspring and the potential benefic effects of fish oil (FO) (n-3 polyunsaturated fatty acid source). METHODS AND RESULTS: Female rats received isocaloric, standard diet (STD: 9% fat) or HFD (28.6%) before mating, and throughout pregnancy and lactation. After weaning, male offspring received standard diet and, from 25th to 45th day, received oral administration of soybean oil (SO) or FO. HFD offspring showed higher body weight and adiposity, which was not attenuated by FO. In STD offspring, FO reduced serum triglyceride and cholesterol, as expected, but not in HFD offspring. Liver of HFD offspring groups showed increased free cholesterol and FO-treated HFD group showed lower expression of Abcg8, suggesting decreased cholesterol biliary excretion. HFD offspring presented higher hepatic expression of lipogenic markers, Srebf1 mRNA and acetyl CoA carboxylase (ACC). Serum n-3 PUFA were decreased in FO-treated HFD compared to FO-treated STD offspring, which may explain the reduced hypolipidemic FO effect. CONCLUSION: Maternal HFD impaired the ability of FO to reduce adiposity and serum lipids in adolescent offspring, suggesting a potential predisposition to future development of metabolic disorders.

Maternal high-fat diet during lactation increases Kiss1 mRNA expression in the arcuate nucleus at weaning and advances puberty onset in female rats.

Nutrition has significant influences on the development of reproductive functions. Post-weaning manipulation of nutritional status has been shown to alter puberty onset accompanied by changes in the expression of kisspeptin, a neuropeptide encoded by the Kiss1 gene which plays important roles in pubertal development. However, information about the influence of overnutrition during early development is sparse. In this study, we examined pubertal development and Kiss1 mRNA expression in female pups reared by dams fed a high-fat diet (HFD) during lactation. Maternal HFD significantly increased body weight and accelerated puberty onset of female offspring. The number of Kiss1-expressing neurons in the arcuate nucleus (ARC) at weaning was significantly greater in pups of HFD-fed dams than in pups of dams fed a normal diet (ND), whereas no significant difference was observed in the anteroventral periventricular nucleus, the other Kiss1-expressing nucleus. Because adipocyte size and serum leptin level were increased in HFD offspring, we examined the effects of exogenous leptin during the pre-weaning period on Kiss1 expression. Unexpectedly, exogenous leptin had no effect on Kiss1 expression. In summary, we demonstrate that a maternal HFD during the early postnatal period induces increased Kiss1 expression in the ARC and early puberty onset in female offspring.

Dieta hiperlipídica materna e pós-natal promove remodelamento adverso do fígado, pâncreas e tecido adiposo na prole / Maternal and postnatal high-fat diet and promotes adverse remodeling of the liver, pancreas and adipose tissue in offspring

A dieta hiperlipídica (high-fat, HF) materna durante a gestação e/ou lactação aumenta a susceptibilidade da prole para o desenvolvimento de doenças crônicas na fase adulta. Verificar a hipótese que a ingestão materna de dieta HF nos períodos críticos de desenvolvimento (gestação e/ou lactação) predispõe à doença não alcoólica do fígado gorduroso e alterações pancreáticas e no tecido adiposo de camundongos machos adultos. Camundongos C57BL/6 fêmeas receberam durante a gestação e/ou lactação dieta padrão (standard chow, SC) ou HF. Filhotes machos foram divididos em cinco grupos: SC - provenientes de mães SC; G - provenientes de mães HF durante a gestação; L - provenientes de mães HF durante a lactação; GL/HF - provenientes de mães HF durante a gestação/lactação, mantendo a mesma dieta HF no período pós-natal (do desmame aos 3 meses de idade); GL - provenientes de mães HF durante a gestação/lactação trocando a dieta para SC no período pós-natal (do desmame aos 3 meses de idade). Foi analisada ao longo do experimento a massa corporal da prole. No sacrifício (3 meses), o fígado, o pâncreas e a gordura epididimária foram removidos, pesados e processados e o sangue foi coletado para análise bioquímica. Ao nascimento e ao desmame, filhotes GL/HF foram mais pesados (+6% e +44%, p<0,05, respectivamente) que os filhotes SC. Os filhotes G apresentaram resistência à insulina e menor expressão do transportador de glicose no fígado (GLUT-2). A esteatose hepática foi observada nos grupos G, L, GL e principalmente nos filhotes do grupo GL/HF. A expressão hepática da proteína ligante de elementos regulatórios de esteróis (SREBP-1c) estava aumentada nos filhotes G, GL e GL/HF. Os filhotes G, GL e GL/HF apresentaram hipertrofia da ilhota pancreática e dos adipócitos quando comparados com o grupo SC. O consumo de dieta HF durante a gestação mostra-se ser o período mais prejudicial para os filhotes adultos de camundongos. A programação metabólica por dieta HF ...

Maternal high-fat diet (HF) during gestation and/or lactation period increases the susceptibility to development of chronic disease in offspring adult life. This work aimed to verify the hypothesis that maternal intake of high-fat diet in critical periods of pregnancy and/or suckling period predisposes to non alcoholic fatty liver disease, pancreatic and adipose tissue alterations in adulthood mice offspring. C57BL/6 female mice were fed, during gestation and/or lactation phases, with standard chow (SC) of HF diet. Male pups were divided into 5 groups: SC - from SC fed dam; G - from HF fed dam during gestation period; L - from HF fed dam during lactation period; GL - from HF fed dam during gestation and lactation periods and GL/HF - from HF fed dam during gestation and lactation, maintaining HF diet from post-weaning to adulthood. We analyzed body mass in all experiment, and at the euthanasia (3 mo-old), liver, pancreas and adipose tissue were removed, weighted and embedded. Blood was collected to biochemical analyses. At birth and at weaning, GL/HF pups were heavier than SC pups (+6% and +44%, p<0.05, respectively). G offspring showed insulin resistance and lower glucose transporter-2 expression (GLUT-2). Hepatic steatosis was present in G, L, GL and mainly in GL/HF offspring. Sterol regulatory element-binding protein-1c (SREBP-1c) expression was higher in G, GL and GL/HF offspring. It is important to mention that pancreatic islet hyperthophy and adipocyte hypertrophy were affected in G, GL and GL/HF offspring in comparison to SC. HF diet administration during gestation period is worse than lactation period. Furthermore, this type of programming by HF predisposes to adverse remodeling in liver, pancreas and adipose tissue in adult mice offspring