β hydroxybutyrate levels in serum and cerebrospinal fluid under ketone body metabolism in rats

Abstract

A high-fat, low-carbohydrate diet (KD) or calorie restriction in the form of every-other-day fasting (EODF) results in ketone body metabolism with an increasing β-hydroxybutyrate (βOHB) level. Previous studies have supported that a KD and EODF have a neuroprotective effect. However, the βOHB levels in the cerebrospinal fluid (CSF) resulting from a KD and EODF remain unknown. The aim of this study was to detect βOHB levels in rats fed a KD, EODF diet, and every-other-day ketogenic diet (EODKD) and to compare the serum βOHB level with the CSF βOHB level. Twenty-four male Sprague-Dawley rats were randomly divided into KD, EODF, EODKD, and standard diet (SD) groups. A customized food with a ratio of carbohydrates to fats of 1:4 was used in the KD and EODKD groups. The βOHB level was measured using ELISA kits in 200 µl serum and 100 µl CSF samples for each rat after feeding for 2 weeks. The KD, EODF, and EODKD resulted in a significant increase in βOHB levels in both the serum and CSF. The βOHB levels in the EODKD group were the highest. The CSF βOHB level was, on average, 69% of the serum βOHB level. There was a positive correlation between the overall βOHB levels in serum and that in cerebrospinal fluid. This study demonstrated that the KD, EODF, and EODKD resulted in ketone body metabolism, as the βOHB levels increased significantly compared with those resulting from the standard diet. Our results suggested that the serum βOHB level was an indicator of the CSF βOHB level, and that the EODKD was an effective diet to enhance ketogenic metabolism.

Salt-Responsive Metabolite, β-Hydroxybutyrate, Attenuates Hypertension

“…βOHB is known to lower inflammatory responses ( Newman and Verdin, 2014 , 2017 ; Roberts et al, 2017 ; Veech et al, 2017 ; Wang et al, 2017 ; Youm et al, 2015 ), and previous studies implicate the immune system in salt-sensitive hypertension via the exaggeration of the pro-inflammatory T cell function ( De Miguel et al, 2010 , 2015 ; Maalouf et al, 2009 ; Mattson, 2014 ; Mattson et al, 2006 ; Rudemiller et al, 2014 ; Wu et al, 2013 ). Therefore, to delineate the mechanism by which βOHB lowers salt-sensitive hypertension, we focused on kidney function in hypertension and examined the status of molecules associated with salt-responsive Th17 activation.…”

“…Similarly, calorie restriction, although not widely recommended for patients, is also documented to lower hypertension ( Dolinsky et al, 2010 ; Melo et al, 2016 ). Interestingly, both exercise and calorie-restriction are associated with increased circulating levels of ketone bodies such as β-Hydroxybutyrate (βOHB) ( Evans et al, 2017 ; Mahoney et al, 2006 ; Newman and Verdin, 2017 ; Sutton et al, 2018 ; Veech et al, 2017 ; Wang et al, 2017 ). βOHB is produced predominantly in the liver, transported to extrahepatic tissues, and traditionally recognized as a vital alternative metabolic fuel during times of starvation ( Newman and Verdin, 2014 ).…”

Differential Ketogenic Diet-Induced Shift in CSF Lipid/Carbohydrate Metabolome of Pediatric Epilepsy Patients With Optimal Vs. No Anticonvulsant Response

“…As expected, ketone bodies (-hydroxybutyrate and acetoacetate) were elevated and glucose was lowered during KD treatment; however, all these responses were significantly smaller in the patients with no clinical response vs. those with optimal response (Figure 2). Serum levels of hydroxybutyrate during KD were also significantly lower in patients with no clinical response (3.2±0.4 mM) vs. those with optimal response (5.2±0.1 mM, p < 0.01), expected as CSF ketone body levels track blood levels [36][37][38][39][40].…”

Intermittent Fasting Protects against Alzheimer’s Disease Possible through Restoring Aquaporin-4 Polarity

“…ADF was also found to play a role in protecting against the increase of Aβ deposition in the brains of APP/PS1 mice. As is well-known, ADF results in an increase in the serum level of the ketone body ( Robinson and Williamson, 1980 ; Wang et al, 2017 ). The increased ketone body by fasting or ketogenic diet is remarkably effective in managing intractable seizures in children.…”

“…Some researchers have recognized the beneficial effects of intermittent fasting (IF) against AD ( Stewart et al, 1989 ; Halagappa et al, 2007 ). What is more, IF results in ketone body metabolism and an increase in β-hydroxybutyrate (βOHB; a major component of ketone bodies) level in blood ( Robinson and Williamson, 1980 ; Wang et al, 2017 ). βOHB has been reported to traverse the blood–brain barrier and significantly inhibit HDAC3 expression as an endogenous pan HDACs inhibitor ( Shimazu et al, 2013 ).…”