Increased hepatic fatty acid polyunsaturation precedes ectopic lipid deposition in the liver in adaptation to high-fat diets in mice

Soares, Ana Francisca; Duarte, João M. N.; Gruetter, Rolf

doi:10.1007/s10334-017-0654-8

Cited by 18 publications

(27 citation statements)

References 54 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Mice were randomly split in three groups ( n = 11/group), and dietary interventions started after 1 week of acclimatization to the facility, i.e., at 3 months of age. During 6 months, mice were fed standardized diets containing 10%, 45%, or 60% of kilocalories from lard-based fat (D12450B, D12451, D12492, Research Diets, New Brunswick, NJ, United States), as previously detailed (Soares et al, 2018). Food and tap water were provided ad libitum .…”

Section: Methodsmentioning

confidence: 99%

“…In the present study, we tested the hypothesis that the severity of the metabolic syndrome is related to the degree of neurochemical alterations, as well as brain function deficits. For that, mice were fed diets containing different amounts of fat during 6 months, which lead to different degrees of glucose intolerance and insulin resistance (Soares et al, 2018). We then evaluated spatial memory performance, metabolic profiles of the hippocampus, cortex and hypothalamus, and levels of proteins specific to synaptic and glial compartments.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Neurochemical Modifications in the Hippocampus, Cortex and Hypothalamus of Mice Exposed to Long-Term High-Fat Diet

et al. 2019

Self Cite

View full text Add to dashboard Cite

Metabolic syndrome and diabetes impact brain function and metabolism. While it is well established that rodents exposed to diets rich in saturated fat develop brain dysfunction, contrasting results abound in the literature, likely as result of exposure to different high-fat diet (HFD) compositions and for varied periods of time. In the present study, we investigated alterations of hippocampal-dependent spatial memory by measuring Y-maze spontaneous alternation, metabolic profiles of the hippocampus, cortex and hypothalamus by 1H magnetic resonance spectroscopy (MRS), and levels of proteins specific to synaptic and glial compartments in mice exposed for 6 months to different amounts of fat (10, 45, or 60% of total energy intake). Increasing the dietary amount of fat from 10 to 45% or 60% resulted in obesity accompanied by increased leptin, fasting blood glucose and insulin, and reduced glucose tolerance. In comparison to controls (10%-fat), only mice fed the 60%-fat diet showed increased fed glycemia, as well as plasma corticosterone that has a major impact on brain function. HFD-induced metabolic profile modifications measured by 1H MRS were observed across the three brain areas in mice exposed to 60%- but not 45%-fat diet, while both HFD groups displayed impaired hippocampal-dependent memory. HFD also affected systems involved in neuro- or gliotransmission in the hippocampus. Namely, relative to controls, 60%-fat-fed mice showed reduced SNAP-25, PSD-95 and syntaxin-4 immunoreactivity, while 45%-fat-fed mice showed reduced gephyrin and syntaxin-4 immunoreactivity. For both HFD levels, reductions of the vesicular glutamate transporter vGlut1 and levels of the vesicular GABA transporter were observed in the hippocampus and hypothalamus, relative to controls. Immunoreactivity against GFAP and/or Iba-1 in the hypothalamus was higher in mice exposed to HFD than controls, suggesting occurrence of gliosis. We conclude that different levels of dietary fat result in distinct neurochemical alterations in the brain.

show abstract

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Neurochemical Modifications in the Hippocampus, Cortex and Hypothalamus of Mice Exposed to Long-Term High-Fat Diet

et al. 2019

Self Cite

View full text Add to dashboard Cite

show abstract

“…Many studies in T2D animal models have employed diets rich in sugar and/or fat in order to induce T2D, namely, highfat diet (HFD), high-sucrose diet, high-fructose diet, or the combination of some of them. Glucose intolerance develops promptly in rodents exposed to HFD, followed by a progressive increase of fasting insulin levels and metabolic derangements such as hepatic lipid accumulation (Soares et al, 2018). We have also recently reported that increasing the dietary amount of lard-based fat from 10 to 45 or 60% leads to slightly different diabetic phenotypes: compared to controls that were exposed to the low-fat diet, increased fed glycemia and plasma corticosterone were observed in mice fed a 60%-but not 45%-fat diet (Lizarbe et al, 2019b).…”

Section: Memory Dysfunction Induced By Diabetogenic Dietsmentioning

confidence: 99%

“…Nevertheless, gene expression profiles in brain microvessels isolated from models of diabetes point toward deregulated expression of genes related to angiogenesis, inflammation, vasoconstriction and vasodilation, and platelet activation pathways (Rom et al, 2019). Proteomic analyses suggest impaired metabolic activity in microvessels from the cerebral cortex of HFD-exposed mice compared to controls (Ouyang et al, 2014), even though HDF exposure results in limited increases of blood glucose levels (Soares et al, 2018;Lizarbe et al, 2019b). Such alterations are likely to impact brain perfusion and to limit nutrient delivery for fueling neuronal energetics (Glaser et al, 2012;Bangen et al, 2018).…”

Section: Hyperglycemia and Brain Glucose Toxicitymentioning

confidence: 99%

Brain Metabolism Alterations in Type 2 Diabetes: What Did We Learn From Diet-Induced Diabetes Models?

García-Serrano

Duarte

2020

Front. Neurosci.

Self Cite

View full text Add to dashboard Cite

Type 2 diabetes (T2D) is a metabolic disease with impact on brain function through mechanisms that include glucose toxicity, vascular damage and blood-brain barrier (BBB) impairments, mitochondrial dysfunction, oxidative stress, brain insulin resistance, synaptic failure, neuroinflammation, and gliosis. Rodent models have been developed for investigating T2D, and have contributed to our understanding of mechanisms involved in T2D-induced brain dysfunction. Namely, mice or rats exposed to diabetogenic diets that are rich in fat and/or sugar have been widely used since they develop memory impairment, especially in tasks that depend on hippocampal processing. Here we summarize main findings on brain energy metabolism alterations underlying dysfunction of neuronal and glial cells promoted by diet-induced metabolic syndrome that progresses to a T2D phenotype.

show abstract

“…(2 g/kg; prepared as 20% (w/v) solution in sterile saline, BRAUN, Melsungen, Germany). Glycaemia 6 was monitored with a glucometer (Accu-check Aviva, Roche, Stockholm, Sweden) from 1-µL tail tip blood samples before the glucose load, and afterwards at 15, 30, 60, 90 and 120 minutes (Soares et al, 2018). A 20-µL blood sample was collected from the saphenous vein for fasting insulin quantification (ELISA kit #10-1247-01 from Mercodia, Uppsala, Sweden).…”

Section: Glucose Tolerance Test (Gtt)mentioning

confidence: 99%

A glucose-stimulated BOLD fMRI study of hypothalamic dysfunction in mice fed a high-fat and high-sucrose diet

Mohr

García-Serrano

Vieira

et al. 2020

Preprint

View full text Add to dashboard Cite

Running headline: Hypothalamic fMRI in diet-induced obese miceAbbreviations: AgRP, agouti-related peptide; AMPK, AMP-activated protein kinase; ARC, arcuate nucleus; BOLD, blood oxygen level-dependent; CART, cocaine and amphetamine regulated transcript; CREB, cAMP response element-binding protein; DMN, dorsomedial nucleus; fMRI, functional magnetic resonance imaging; FOV, field of view; LH, lateral hypothalamus; MC4R, melanocortin 4 receptor; NPY, neuropeptide Y; POMC, pro-opiomelanocortin; PVN, paraventricular nucleus; T2D, type 2 diabetes; TE, echo time; TR, repetition time; VMN, ventromedial nucleus; VOI, volume of interest. AbstractThe hypothalamus is the central regulator of energy homeostasis. Hypothalamic neuronal circuits are disrupted upon overfeeding, and play a role in the development of metabolic disorders.While mouse models have been extensively employed for understanding mechanisms of hypothalamic dysfunction, functional magnetic resonance imaging (fMRI) on hypothalamic nuclei has been challenging. We implemented a robust glucose-induced fMRI paradigm that allows to repeatedly investigate hypothalamic responses to glucose. This approach was used to test the hypothesis that hypothalamic nuclei functioning is impaired in mice exposed to a high-fat and highsucrose diet (HFHSD) for 7 days. The blood oxygen level-dependent (BOLD) fMRI signal was measured from brains of mice under light isoflurane anaesthesia, during which a 2.6 g/kg glucose load was administered. The mouse hypothalamus responded to glucose but not saline administration with a biphasic BOLD fMRI signal reduction. Relative to controls, HFHSD-fed mice showed attenuated or blunted responses in arcuate nucleus, lateral hypothalamus, ventromedial nucleus and dorsomedial nucleus, but not in paraventricular nucleus. In sum, we have developed an fMRI paradigm that is able to determine dysfunction of glucose-sensing neuronal circuits within the mouse hypothalamus in a non-invasive manner.

show abstract

Increased hepatic fatty acid polyunsaturation precedes ectopic lipid deposition in the liver in adaptation to high-fat diets in mice

Abstract: A similar adaptation of hepatic lipids to both fasting and an HFD suggests common mechanisms of lipid trafficking from adipose tissue to the liver. Altered hepatic lipid handling with fasting indicates imperfect metabolic recovery from HFD exposure.

Cited by 18 publications

References 54 publications

Neurochemical Modifications in the Hippocampus, Cortex and Hypothalamus of Mice Exposed to Long-Term High-Fat Diet

Neurochemical Modifications in the Hippocampus, Cortex and Hypothalamus of Mice Exposed to Long-Term High-Fat Diet

Brain Metabolism Alterations in Type 2 Diabetes: What Did We Learn From Diet-Induced Diabetes Models?

A glucose-stimulated BOLD fMRI study of hypothalamic dysfunction in mice fed a high-fat and high-sucrose diet

Contact Info

Product

Resources

About