Diet-induced ketosis increases capillary density without altered blood flow in rat brain

2007 ◽  
Vol 292 (6) ◽  
pp. E1607-E1615 ◽  
Author(s):  
Michelle A. Puchowicz ◽  
Kui Xu ◽  
Xiaoyan Sun ◽  
Andre Ivy ◽  
Doug Emancipator ◽  
...  

It is recognized that ketone bodies, such as R-β-hydroxybutyrate (β-HB) and acetoacetate, are energy sources for the brain. As with glucose metabolism, monocarboxylate uptake by the brain is dependent on the function and regulation of its own transporter system. We concurrently investigated ketone body influx, blood flow, and regulation of monocarboxylate transporter (MCT-1) and glucose transporter (GLUT-1) in diet-induced ketotic (KG) rat brain. Regional blood-to-brain β-HB influx (μmol·g−1·min−1) increased 40-fold with ketosis (4.8 ± 1.8 plasmaβ-HB; mM) in all regions compared with the nonketotic groups (standard and no-fat diets); there were no changes in regional blood flow. Immunohistochemical staining revealed that GLUT-1 density (number/mm2) in the cortex was significantly elevated (40%) in the ketotic group compared with the standard and no-fat diet groups. MCT-1 was also markedly (3-fold) upregulated in the ketotic group compared with the standard diet group. In the standard diet group, 40% of the brain capillaries stained positive for MCT-1; this amount doubled with the ketotic diet. Western blot analysis of isolated microvessels from ketotic rat brain showed an eightfold increase in GLUT-1 and a threefold increase in MCT-1 compared with the standard diet group. These data suggest that diet-induced ketosis results in increased vascular density at the blood-brain barrier without changes in blood flow. The increase in extraction fraction and capillary density with increased plasma ketone bodies indicates a significant flux of substrates available for brain energy metabolism.

2015 ◽  
Vol 1 (2) ◽  
Author(s):  
Philips Onggowidjaja ◽  
M. Nurhalim Shahib

This research was to evaluate the influence of common carp meat diet on brain index and  gene NR2B expression of  Swiss Webster mice cerebrum.  The gene expression and performance of ion Ca2+ channel in neuron are influenced by Glycine and Glutamic Acid, which present in relatively high quantities in common carp meat.  Eighteen male mice were divided into 3 diet groups, the standard pellet, 120 mg and 480 mg common carp meat/day.  The brain index differences among groups were analyzed using ANOVA test (p≤0,05) and LSD.  The total RNA of 5 mg mouse cerebrum was isolated, followed by RT-PCR; the DNA quantities were predicted using Geldoc instrument, then were analyzed using ANOVA test (p≤0,05).  The 120 mg diet group brain index did not show difference (p=0,284) against the standard diet group, while the 480 mg diet group showed the increase compared to the standard (p=0,034) and 120 mg diet groups (p=0,004).  No DNA quantity differences of all groups (p=0,195).  It was concluded, the 480 mg common carp meat/ day diet increased the brain index of Swiss Webster mice, while the 120 mg and 480 mg common carp/day diets did not influence the gene NR2B expression of Swiss Webster mice cerebrum. Keywords : brain index, gene NR2B expression, common carp meat diet


Nutrients ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 2681
Author(s):  
Viggiano ◽  
Meccariello ◽  
Santoro ◽  
Secondulfo ◽  
Operto ◽  
...  

The antiepileptic effect of ketogenic diets is acknowledged but its mechanism of action is poorly understood. The present work aimed to evaluate possible effects of a calorie-restricted ketogenic diet (CRKD) on brain growth and angiogenesis in normal prepubertal rats. Two groups of prepubertal rats were fed with a standard diet (group 1) or a CRKD (group 2) for ten weeks. Then, rats were sacrificed and the thickness for the following structures was evaluated by histology: (1) cerebral cortex, (2) deep cerebral white matter, and (3) substantia nigra. The capillary density was also evaluated within: (1) cerebral cortex, (2) dentate gyrus of the hippocampus, (3) periaqueductal grey matter, and (4) substantia nigra. The results showed a smaller thickness of all the areas examined and a reduced capillary density within the cerebral cortex in the CRKD-treated group compared to the control group. These findings suggest an association between reduced angiogenesis within the cerebral cortex and the antiepileptic effects of CRKD.


1984 ◽  
Vol 4 (2) ◽  
pp. 275-283 ◽  
Author(s):  
Shigeharu Takagi ◽  
Kazumasa Ehara ◽  
Peter J. Kenny ◽  
Ronald D. Finn ◽  
Paresh J. Kothari ◽  
...  

No method has been reported for measuring CBF, repeatedly and noninvasively, in the rat brain. A new method is described, which is noninvasive to the brain, skull, or cervical large vessels. Two pairs of coincidence detectors were positioned, one over the rat brain and the other at the loop of a catheter inserted into the femoral artery. The coincidence head curve and arterial curve were recorded after intravenous injection of 1-[11C]butanol in 15 rats. CBF was calculated by one-compartment curve fitting (CBFo) from 1-min data and with the recirculation corrected height/area method from 3-min data (CBFh · 3min) and 5-min data (CBFh · 5min). CBFo agreed well with CBFh · 5min, although a slight overestimation was observed in CBFh · 3min. The normal CBFo in the normocapnic group (n = 6, paco2 36.7 ± 2.3 mm Hg) was 1.76 ± 0.49 ml/g min (mean ± SD). A good correlation was observed between CBFo ( y) and Paco2 ( x), and the regression line was y = 0.0629 x – 0.715 (r = 0.88, p < 0.0001). We concluded that this method gives the stable blood flow values noninvasively and with a minimum loss of blood (<0.28 ml per measurement). Applications of this method include activation studies, studies on the effect of drugs and treatments, and water and oxygen extraction fraction studies using different tracers in the same rat.


2020 ◽  
Vol 54 (6) ◽  
pp. 536-545
Author(s):  
Jussi Helppi ◽  
Ronald Naumann ◽  
Oliver Zierau

One of the most commonly used protein sources in rodent diets is soy, which is naturally rich in phytoestrogens. Although phytoestrogens have shown potential health benefits in humans, they may also have the ability to disrupt reproduction. Consequently, there has been a tendency to try to exclude them from rodent diets. In the current study, we investigated whether phytoestrogen content in the mouse diet could affect reproduction in mice used as embryo donors. Donor mice (C57BL/6JOlaHsd) were maintained with three different diets: high phytoestrogen (ca. 400 mg/kg genistein), low phytoestrogen (ca. 10 mg/kg genistein) and standard breeding diet (ca. 120 mg/kg genistein). Mice fed a high phytoestrogen diet had a high yield of plugs, embryos, and injectable embryos, as well as producing good quality embryos. Results from donor mice fed a low phytoestrogen diet were consistently but only slightly inferior, whereas mice fed a standard diet performed the poorest. Interestingly, the largest number of born and weaned offspring were observed when recipient females received embryos from the standard diet group. Sperm yield and quality of stud males did not differ between the groups. We surmize that for experimental endpoints requiring fertilized embryos it may be more beneficial to feed mice a diet containing phytoestrogen, but if the goal is to produce transgenic mice, a diet high in phytoestrogen may be inadvisable. In conclusion, care should be taken when selecting a diet for experimental mouse colonies as phytoestrogen could influence the study outcome.


Author(s):  
Kui Xu ◽  
Joseph C. LaManna ◽  
Michelle A. Puchowicz

The brain is normally completely dependent on glucose, but is capable of using ketones as an alternate energy source, as occurs with prolonged starvation or chronic feeding of a ketogenic diet. Research has shown that ketosis is neuroprotective against ischemic insults in rodents. This review focuses on investigating the mechanistic links to neuroprotection by ketosis in the aged. Recovery from stroke and other pathophysiological conditions in the aged is challenging. Cerebral metabolic rate for glucose, cerebral blood flow, and the defenses against oxidative stress are known to decline with age, suggesting dysfunction of the neurovascular unit. One mechanism of neuroprotection by ketosis involves succinate-induced stabilization of hypoxic inducible factor-1alpha (HIF1α‎) and its downstream effects on intermediary metabolism. The chapter hypothesizes that ketone bodies play a role in the restoration of energy balance (stabilization of ATP supply) and act as signaling molecules through the up-regulation of salvation pathways targeted by HIF1α‎.


2013 ◽  
Vol 33 (8) ◽  
pp. 1307-1311 ◽  
Author(s):  
Yifan Zhang ◽  
Youzhi Kuang ◽  
Kui Xu ◽  
Donald Harris ◽  
Zhenghong Lee ◽  
...  

The brain is dependent on glucose as a primary energy substrate, but is capable of utilizing ketones such as β-hydroxybutyrate and acetoacetate, as occurs with fasting, starvation, or chronic feeding of a ketogenic diet. The relationship between changes in cerebral metabolic rates of glucose (CMRglc) and degree or duration of ketosis remains uncertain. To investigate if CMRglc decreases with chronic ketosis, 2-[18F]fluoro-2-deoxy-D-glucose in combination with positron emission tomography, was applied in anesthetized young adult rats fed 3 weeks of either standard or ketogenic diets. Cerebral metabolic rates of glucose (μmol/min per 100 g) was determined in the cerebral cortex and cerebellum using Gjedde-Patlak analysis. The average CMRglc significantly decreased in the cerebral cortex (23.0 ±4.9 versus 32.9 ±4.7) and cerebellum (29.3 ± 8.6 versus 41.2 ±6.4) with increased plasma ketone bodies in the ketotic rats compared with standard diet group. The reduction of CMRg|c in both brain regions correlates linearly by ∼9% for each 1 mmol/L increase of total plasma ketone bodies (0.3 to 6.3 mmol/L). Together with our meta-analysis, these data revealed that the degree and duration of ketosis has a major role in determining the corresponding change in CMRglc with ketosis.


2018 ◽  
Author(s):  
Xinanbei Liu ◽  
Na Li ◽  
Yueyue Shu ◽  
Yiran Sun ◽  
Yu Li ◽  
...  

ABSTRACTIdesia polycarpa Maxim. var. vestita Diels (Idesiapolycarpa), which is widely distributed in south China, is still underexplored. This study applied Idesia polycarpa defatted fruit (IPF) and Candida utilis to the feed of laying quails using solid-state fermentation. In comparison to the standard diet group, birds fed with mixture of IPF and Candida utilis (MIC) showed better production capacity, and the ML group (1% MIC added) achieved the greatest egg mass (9.77 on average; P<0.01) and laying rate (87.7% on average; P<0.01). Compared to the standard diet group, the cholesterol content was lower in both the ML (1% MIC addition groups) and IL (1% IPF addition groups), and 5% MIC added group had higher n-3 polyunsaturated fatty acid content. Furthermore, birds given the MIC dietary supplement showed a thicker jejunum wall than the standard diet group. In addition, the related mRNA expression of SRBEP-1, SREBP-2, ATGL, APOVLDL-II which are involved in the fatty acid and cholesterol biosynthesis suggested that the addition of Candida utilis could effectively improve the production capacity of laying quails while decrease the negative effects of IPF. This work also demonstrates how MIC can be applied to improve the production of laying quails.


1989 ◽  
Vol 256 (6) ◽  
pp. E805-E810 ◽  
Author(s):  
C. Redies ◽  
L. J. Hoffer ◽  
C. Beil ◽  
E. B. Marliss ◽  
A. C. Evans ◽  
...  

In prolonged fasting, the brain derives a large portion of its oxidative energy from the ketone bodies, beta-hydroxybutyrate and acetoacetate, thereby reducing whole body glucose consumption. Energy substrate utilization differs regionally in the brain of fasting rat, but comparable information has hitherto been unavailable in humans. We used positron emission tomography (PET) to study regional brain glucose and oxygen metabolism, blood flow, and blood volume in four obese subjects before and after a 3-wk total fast. Whole brain glucose utilization fell to 54% of control (postabsorptive) values (P less than 0.002). The whole brain rate constant for glucose tracer phosphorylation fell to 51% of control values (P less than 0.002). Both parameters decreased uniformly throughout the brain. The 2-fluoro-2-deoxy-D-glucose lumped constant decreased from a control value of 0.57 to 0.43 (P less than 0.01). Regional blood-brain barrier transfer coefficients for glucose tracer, regional oxygen utilization, blood flow, and blood volume were unchanged.


Parasitology ◽  
2006 ◽  
Vol 134 (1) ◽  
pp. 121-127 ◽  
Author(s):  
S. PETKEVIČIUS ◽  
L. E. THOMSEN ◽  
K. E. BACH KNUDSEN ◽  
K. D. MURRELL ◽  
A. ROEPSTORFF ◽  
...  

The objective of this experiment was to investigate the potential influence of inulin on the establishment of new and patent infections ofTrichuris suisin growing pigs. Two experimental diets were formulated based on barley flour with either added insoluble fibre from oat husk (Diet 1) or a pure inulin (16%) supplementation (Diet 2). Twenty-eight 10-week-old pigs were divided randomly into 4 groups (Groups 1–4) each of 7 pigs. After 3 weeks adaptation to the experimental diets all pigs were infected with a single dose of 2000 infectiveT. suiseggs. Group 1 was fed Diet 1 until 7 weeks post-infection (p.i.) and Group 3 until 9 weeks p.i., Group 2 was fed Diet 2 until 7 weeks p.i., Group 4 was fed Diet 1 until week 7 p.i. and was switched-over from Diet 1 to Diet 2 until week 9 p.i. Seven weeks p.i. pigs in Groups 1 and 2 were slaughtered, and pigs in Groups 3 and 4 were slaughtered at 9 weeks p.i.Trichuris suisworm burdens were determined for all pigs. Inulin-fed pigs (Group 2) exhibited an 87% reduction in EPG, compared to the pigs on standard diet (Group 1) (P<0·0001). The number of worms recovered at week 7 p.i. from pigs on the inulin diet (Group 2) was significantly reduced by 71%, compared to the pigs on standard diet (Group 1) (P<0·01). At week 9, worm recovery in pigs on the inulin diet switch protocol (Group 4) was reduced by 47% compared to the control pigs in Group 3 (P<0·01). Further, the inulin-fed pigs exhibited a significant reduction in female worm fecundity and worm large intestine location was more distal compared to those from pigs on standard diet. These results demonstrate that inclusion of the highly degradable fructose polymer inulin in the diet leads to significant reductions inT. suisestablishment, egg excretion, and female worm fecundity and can be used as a treatment for patent infections.


2010 ◽  
Vol 30 (10) ◽  
pp. 1549-1560 ◽  
Author(s):  
Ibtissem Ben Amara ◽  
Ahmed Hakim ◽  
Afef Troudi ◽  
Nejla Soudani ◽  
Fatma Ayadi Makni ◽  
...  

The present study investigates the potential ability of selenium, considered as an antioxidant with pharmacological property to alleviate oxidative stress and hematological parameter disorders induced by methimazole, an antithyroid drug. Pregnant Wistar rats were randomly divided into four groups of six each: group I served as negative control and received a standard diet; group II received 250 mg/L of methimazole in drinking water and a standard diet; group III received both methimazole (250 mg/L, orally) and selenium (0.5 mg/kg of diet) supplemented to the standard diet; group IV served as positive control and received a supplement of selenium in the diet (0.5 mg/kg of diet) as sodium selenite (Na2SeO3). Treatment was started from the 14th day of pregnancy until day 14 after delivery. Methimazole reduced the number of red blood cells, hemoglobin concentration and hematocrit in mothers and their pups. Besides, plasma iron, vitamins B9, B12, C and E levels were reduced. Lipid peroxidation increased, objectified by high malondialdehyde levels and lactate dehydrogenase activity in plasma, while glutathione, glutathione peroxidase, superoxide dismutase and catalase activities showed a significant decline. Co-administration of selenium through diet improved all the parameters cited above. It can be concluded that the administration of selenium alleviates methimazole-induced toxicity, thus demonstrating its antioxidant efficacy.


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