High-fat diet transition reduces brain DHA levels associated with altered brain plasticity and behaviour.
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ABSTRACT:
SUBMITTER: Sharma S
PROVIDER: S-EPMC3362800 | biostudies-other | 2012
REPOSITORIES: biostudies-other
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Project description: Not available
| S-EPMC11343842 | biostudies-literature
Project description:SCOPE:Dietary fat composition can modulate gene expression in peripheral tissues in obesity. Observations of the dysregulation of growth hormone (GH) in obesity indicate that these effects extend to the hypothalamic-pituitary (H-P) axis. The authors thus determine whether specific high fat (HF) diets influence the levels of Gh and other key gene transcripts in the H-P axis. METHODS AND RESULTS:C57BL/6 mice are fed a lean control diet or a HF diet in the absence or presence of OA, EPA, or DHA ethyl esters. Comparative studies are conducted with menhaden fish oil. The HF diet lowered pituitary Gh mRNA and protein levels, and cell culture studies reveal that elevated insulin and glucose can reduce Gh transcripts. Supplementation of the HF diet with OA, EPA, DHA, or menhaden fish oil do not improve pituitary Gh levels. The HF diet also impaired the levels of additional genes in the pituitary and hypothalamus, which are selectively rescued with EPA or DHA ethyl esters. The effects of EPA and DHA are more robust relative to fish oil. CONCLUSION:A HF diet can affect H-P axis transcription, which can be mitigated in some genes by EPA and DHA, but not fish oil in most cases.
| S-EPMC6319960 | biostudies-literature
Project description:Insulin resistance and other features of the metabolic syndrome are increasingly recognized for their effects on cognitive health. To ascertain mechanisms by which this occurs, we fed mice a very high fat diet (60% kcal by fat) for 17days or a moderate high fat diet (HFD, 45% kcal by fat) for 8weeks and examined changes in brain insulin signaling responses, hippocampal synaptodendritic protein expression, and spatial working memory. Compared to normal control diet mice, cerebral cortex tissues of HFD mice were insulin-resistant as evidenced by failed activation of Akt, S6 and GSK3? with ex-vivo insulin stimulation. Importantly, we found that expression of brain IPMK, which is necessary for mTOR/Akt signaling, remained decreased in HFD mice upon activation of AMPK. HFD mouse hippocampus exhibited increased expression of serine-phosphorylated insulin receptor substrate 1 (IRS1-pS(616)), a marker of insulin resistance, as well as decreased expression of PSD-95, a scaffolding protein enriched in post-synaptic densities, and synaptopodin, an actin-associated protein enriched in spine apparatuses. Spatial working memory was impaired as assessed by decreased spontaneous alternation in a T-maze. These findings indicate that HFD is associated with telencephalic insulin resistance and deleterious effects on synaptic integrity and cognitive behaviors.
| S-EPMC4083060 | biostudies-literature
Project description:To investigate the effect of docosahexaenoic acid (DHA) without other highly unsaturated fatty acids (HUFA) on n-3 and n-6 essential fatty acid (EFA) metabolism and fatty acid composition in mammals, a stable isotope tracer technique was used in adult rats fed diets with or without 1.3% of algal DHA in a base diet containing 15% of linoleic acid and 3% of alpha-linolenic acid over 8 weeks. The rats were administered orally a mixed oil containing 48 mg/kg body weight of deuterated linoleic and alpha-linolenic acids and euthanized at 4, 8, 24, 96, 168, 240, 360 and 600 h after administration of the isotopes. Fatty acid compositions and the concentrations of deuterated precursors and their respective metabolites were determined in rat liver, plasma, heart and brain as a function of time. DHA, docosapentaenoic acid and eicosapentaenoic acid in the n-3 EFA family were significantly increased in all organs tested in the DHA-fed group, ranging from 5% to 200% greater in comparison with the control group. The accumulation of the metabolites, deuterated-DHA and deuterated-docosapentaenoic acid n-6 was greatly decreased by 1.5- to 2.5-fold in the dietary DHA group. In summary, feeding preformed DHA led to a marked increase in n-3 HUFA content of rat organs at the expense of n-6 HUFA and also prevented the accumulation of newly synthesized deuterated end products. This is the first study which has isolated the effects of DHA on the de novo metabolism on both the n-6 and n-3 EFA pathways.
| S-EPMC3075345 | biostudies-literature
Project description:The gut microbiota is important in the occurrence and development of obesity. It can not only via its metabolites, but also through microbiota-gut-brain-liver interactions, directly or indirectly, influence obesity. Quinoa, known as one kind of pseudocereals and weight loss food supplements, has been high-profile for its high nutritional value and broad applications. In this context, we produced high-fat diet-induced (HFD) obese mouse models and assessed the efficacy of quinoa with saponin and quinoa without saponin on obesity. We explored the potential therapeutic mechanisms of quinoa using methods such as 16S rRNA, Western blotting, Immunohistochemical (IHC). Our results indicated that quinoa can improve the obese symptoms significantly on HFD mice, as well as aberrant glucose and lipid metabolism. Further analyses suggest that quinoa can regulate microbiota in the colon and have predominantly regulation on Bacteroidetes, Actinobacteria and Desulfovibrio, meanwhile can decrease the F/B ratio and the abundance of Blautia. Contemporaneously, quinoa can upregulate the expression of TGR5 in the colon and brain, as well as GLP-1 in the colon, liver and brain. while downregulate the expression of TLR4 in the colon and liver, as well as markers of ER stress and oxidative stress in livers and serums. Beyond this, tight junctional proteins in colons and brains are also increased in response to quinoa. Therefore, quinoa can effectively reduce obesity and may possibly exert through microbiota-gut-brain-liver interaction mechanisms. IMPORTANCE Gut microbiota has been investigated extensively, as a driver of obesity as well as a therapeutic target. Studies of its mechanisms are predominantly microbiota-gut-brain axis or microbiota-gut-liver axis. Recent studies have shown that there is an important correlation between the gut-brain-liver axis and the energy balance of the body. Our research focus on microbiota-gut-brain-liver axis, as well as influences of quinoa in intestinal microbiota. We extend this study to the interaction between microbiota and brains, and the result shows obvious differences in the composition of the microbiome between the HFD group and others. These observations infer that besides the neurotransmitter and related receptors, microbiota itself may be a mediator for regulating bidirectional communication, along the gut-brain-liver axis. Taken together, these results also provide strong evidence for widening the domain of applicability of quinoa.
| S-EPMC9241864 | biostudies-literature
Project description:Maternal obesity is associated with lower basal plasma cortisol levels and increased risk of postpartum psychiatric disorders. Given that both obesity and the peripartum period are characterized by an imbalance between adrenocorticotropic hormone (ACTH) and cortisol, we hypothesized that the adrenal glands undergo peripartum-associated plasticity and that such changes would be prevented by a high-fat diet (HFD). Here, we demonstrate substantial peripartum adrenal gland plasticity in the pathways involved in cholesterol supply for steroidogenesis in female rats. In detail, the receptors involved in plasma lipid uptake, low density lipoprotein (LDL) receptor (LDLR) and scavenger receptor class B type 1 (SRB1), are elevated, intra-adrenal cholesterol stores are depleted, and a key enzyme in de novo cholesterol synthesis, hydroxymethylglutaryl coenzyme A reductase (HMGCR), is downregulated; particularly at mid-lactation. HFD prevented the lactation-associated anxiolysis, basal hypercorticism, and exaggerated the corticosterone response to ACTH. Moreover, we show that HFD prevented the downregulation of adrenal cholesterol stores and HMGCR expression, and LDLR upregulation at mid-lactation. These findings show that the adrenal gland is an important regulator of peripartum-associated HPA axis plasticity and that HFD has maladaptive consequences for the mother, partly by preventing these neuroendocrine and also behavioural changes.
| S-EPMC4595833 | biostudies-other
Project description:To maintain homeostasis, the body, including the brain, reprograms its metabolism in response to altered nutrition or disease. However, the consequences of these challenges for the energy metabolism of the different brain cell types remain unknown. Here, we generated a proteome atlas of the major central nervous system (CNS) cell types from young and adult mice, after feeding the therapeutically relevant low-carbohydrate, high-fat ketogenic diet (KD) and during neuroinflammation. Under steady-state conditions, CNS cell types prefer distinct modes of energy metabolism. Unexpectedly, the comparison with KD revealed distinct cell type-specific strategies to manage the altered availability of energy metabolites. Astrocytes and neurons but not oligodendrocytes demonstrated metabolic plasticity. Moreover, inflammatory demyelinating disease changed the neuronal metabolic signature in a similar direction as KD. Together, these findings highlight the importance of the metabolic cross-talk between CNS cells and between the periphery and the brain to manage altered nutrition and neurological disease.
| S-EPMC9481126 | biostudies-literature
Project description:High-fat diet (HFD)-induced obesity is associated with insulin resistance, which may affect brain synaptic plasticity through impairment of insulin-sensitive processes underlying neuronal survival, learning, and memory. The experimental model consisted of 3 month-old C57BL/6J mice fed either a normal chow diet (control group) or a HFD (60% of calorie from fat; HFD group) for 12 weeks. This model was characterized as a function of time in terms of body weight, fasting blood glucose and insulin levels, HOMA-IR values, and plasma triglycerides. IRS-1/Akt pathway was assessed in primary hepatocytes and brain homogenates. The effect of HFD in brain was assessed by electrophysiology, input/output responses and long-term potentiation. HFD-fed mice exhibited a significant increase in body weight, higher fasting glucose- and insulin levels in plasma, lower glucose tolerance, and higher HOMA-IR values. In liver, HFD elicited (a) a significant decrease of insulin receptor substrate (IRS-1) phosphorylation on Tyr608 and increase of Ser307 phosphorylation, indicative of IRS-1 inactivation; (b) these changes were accompanied by inflammatory responses in terms of increases in the expression of NF?B and iNOS and activation of the MAP kinases p38 and JNK; (c) primary hepatocytes from mice fed a HFD showed decreased cellular oxygen consumption rates (indicative of mitochondrial functional impairment); this can be ascribed partly to a decreased expression of PGC1? and mitochondrial biogenesis. In brain, HFD feeding elicited (a) an inactivation of the IRS-1 and, consequentially, (b) a decreased expression and plasma membrane localization of the insulin-sensitive neuronal glucose transporters GLUT3/GLUT4; (c) a suppression of the ERK/CREB pathway, and (d) a substantial decrease in long-term potentiation in the CA1 region of hippocampus (indicative of impaired synaptic plasticity). It may be surmised that 12 weeks fed with HFD induce a systemic insulin resistance that impacts profoundly on brain activity, i.e., synaptic plasticity.
| S-EPMC4449222 | biostudies-literature
Project description:Novel progress has been made to understand the adverse pathophysiology in the pancreas of offspring exposed to overnutrition in utero. Our study is the first to evaluate whether the adverse effects of maternal overnutrition on offspring β-cell function are reversible or preventable through preconception maternal diet interventions. Herein, offspring mice were exposed in utero to one of the following: maternal normal-fat diet (NF group), maternal high-fat diet (HF group) or maternal diet transition from an HF to NF diet 9 weeks before pregnancy (H9N group). Offspring mice were subjected to postweaning HF diet for 12 weeks. HF offspring, but not H9N, displayed glucose intolerance and insulin resistance. HF male offspring had enlarged islet β-cells with reduced β-cell density, whereas, H9N male offspring did not show these changes. Co-immunofluorescent (Co-IF) staining of glucose transporter 2 (Glut2) and insulin (Ins) revealed significantly more Glut2+Ins- cells, indicative of insulin degranulation, in HF male offspring but not H9N. In addition, Co-IF of insulin and p-H3S10 indicated that β cells of HF male offspring, but not H9N, had proliferation defects likely due to inhibited protein kinase B (AKT) phosphorylation. In summary, our study demonstrates that maternal H9N diet effectively prevents functional deterioration of β cells seen in HF male offspring by avoiding β-cell proliferation defects and degranulation.
| S-EPMC7643480 | biostudies-literature
Project description:Apolipoprotein E4 (ApoE4), one of three common isoforms of ApoE, is a major risk factor for late-onset Alzheimer disease (AD). ApoE-deficient mice, as well as mice expressing human ApoE4, display impaired learning and memory functions and signs of neurodegeneration. Moreover, ApoE protects against high-fat (HF) diet induced neurodegeneration by its role in the maintenance of the integrity of the blood-brain barrier. The influence of a HF diet on the progression of AD-like cognitive and neuropathological changes was assessed in wild-type (WT), human ApoE4 and ApoE-knockout (ApoE-/-) mice to evaluate the modulatory role of ApoE in this process. From 12 months of age, female WT, ApoE4, and ApoE-/- mice were fed either a standard or a HF diet (19% butter, 0.5% cholate, 1.25% cholesterol) throughout life. At 15 months of age mice performed the Morris water maze, evaluating spatial learning and memory. ApoE-/- showed increased spatial learning compared to WT mice (p = 0.009). HF diet improved spatial learning in WT mice (p = 0.045), but did not affect ApoE4 and ApoE-/- mice. Immunohistochemical analyses of the hippocampus demonstrated increased neuroinflammation (CD68) in the cornu ammonis 1 (CA1) region in ApoE4 (p = 0.001) and in ApoE-/- (p = 0.032) mice on standard diet. HF diet tended to increase CD68 in the CA1 in WT mice (p = 0.052), while it decreased in ApoE4 (p = 0.009), but ApoE-/- remained unaffected. A trend towards increased neurogenesis (DCX) was found in both ApoE4 (p = 0.052) and ApoE-/- mice (p = 0.068). In conclusion, these data suggest that HF intake induces different effects in WT mice compared to ApoE4 and ApoE-/- with respect to markers for cognition and neurodegeneration. We propose that HF intake inhibits the compensatory mechanisms of neuroinflammation and neurogenesis in aged female ApoE4 and ApoE-/- mice.
| S-EPMC4865084 | biostudies-literature