Hemin Prevents Increased Glycolysis in Macrophages upon Activation: Protection by Microbiota-Derived Metabolites of Polyphenols.

Meat consumption plays a critical role in the development of several types of cancer. Hemin, a metabolite of myoglobin produced after meat intake, has been demonstrated to be involved in the cancer initiation phase. Macrophages are key components of the innate immunity, which, upon activation, can prevent cancer development by eliminating neoplastic cells.

Metabolic Roles of Androgen Receptor and Tip60 in Androgen-Dependent Prostate Cancer.

Androgen receptor (AR)-mediated signaling is essential for the growth and differentiation of the normal prostate and is the primary target for androgen deprivation therapy in prostate cancer. Tat interactive protein 60 kDa (Tip60) is a histone acetyltransferase that is critical for AR activation. It is well known that cancer cells rewire their metabolic pathways in order to sustain aberrant proliferation.

The Molecular Effects of Sulforaphane and Capsaicin on Metabolism upon Androgen and Tip60 Activation of Androgen Receptor.

Androgen receptor (AR) stimulators, such as androgen and Tip60, play a pivotal role in prostatic carcinogenesis as androgen receptor signaling is critical for the growth and transformation of the prostate gland. Moreover, androgen and Tip60 promotes HIF-1α activation, involved in metabolic reprogramming by increasing glycolysis, a hallmark in cancer initiation and development. In this study we evaluated the effect of androgen and Tip60 stimulus in AR pathway activation and HIF-1α stabilization, in terms of proliferation and cell metabolism in androgen-sensitive LNCaP cells.

A pilot study of add-on oral triheptanoin treatment for children with medically refractory epilepsy.

Aim: Despite antiepileptic medication and dietary treatment options available about 45% of children with epilepsy still suffer from uncontrolled seizures. Triheptanoin is an anaplerotic treatment designed to improve energy generation via the Krebs cycle.

Method: For the first time, we evaluated the feasibility, tolerability and efficacy of add-on triheptanoin in 12 patients with medically refractory epilepsy (seven males, five females; min-max: 3-18yr, median 13.

Heptanoate is neuroprotective in vitro but triheptanoin post-treatment did not protect against middle cerebral artery occlusion in rats.

Triheptanoin, the medium-chain triglyceride of heptanoate, has been shown to be anticonvulsant and neuroprotective in several neurological disorders. In the gastrointestinal tract, triheptanoin is cleaved to heptanoate, which is then taken up by the blood and most tissues, including liver, heart and brain. Here we evaluated the neuroprotective effects of heptanoate and its effects on mitochondrial oxygen consumption in vitro.

Triheptanoin protects against status epilepticus-induced hippocampal mitochondrial dysfunctions, oxidative stress and neuronal degeneration.

Triheptanoin, the triglyceride of heptanoate, is anaplerotic (refills deficient tricarboxylic acid cycle intermediates) via the propionyl-CoA carboxylase pathway. It has been shown to be neuroprotective and anticonvulsant in several models of neurological disorders. Here, we investigated the effects of triheptanoin against changes of hippocampal mitochondrial functions, oxidative stress and cell death induced by pilocarpine-induced status epilepticus (SE) in mice.

Sulforaphane Protects against High Cholesterol-Induced Mitochondrial Bioenergetics Impairments, Inflammation, and Oxidative Stress and Preserves Pancreatic -Cells Function.

Cholesterol plays an important role in inducing pancreatic -cell dysfunction, leading to an impaired insulin secretory response to glucose. This study aimed to determine the protective effects of sulforaphane, a natural isothiocyanate Nrf2-inducer, against cholesterol-induced pancreatic -cells dysfunction, through molecular and cellular mechanisms involving mitochondrial bioenergetics. Sulforaphane prevented cholesterol-induced alterations in the coupling efficiency of mitochondrial respiration, improving ATP turnover and spare capacity, and averted the impairment of the electron flow at complexes I, II, and IV.

Alternative Fuels in Epilepsy and Amyotrophic Lateral Sclerosis.

This review summarises the recent findings on metabolic treatments for epilepsy and Amyotrophic Lateral Sclerosis (ALS) in honour of Professor Ursula Sonnewald. The metabolic impairments in rodent models of these disorders as well as affected patients are being discussed. In both epilepsy and ALS, there are defects in glucose uptake and reduced tricarboxylic acid (TCA) cycling, at least in part due to reduced amounts of C4 TCA cycle intermediates.

The deleterious effect of cholesterol and protection by quercetin on mitochondrial bioenergetics of pancreatic β-cells, glycemic control and inflammation: In vitro and in vivo studies.

Studying rats fed high cholesterol diet and a pancreatic β-cell line (Min6), we aimed to determine the mechanisms by which quercetin protects against cholesterol-induced pancreatic β-cell dysfunction and impairments in glycemic control. Quercetin prevented the increase in total plasma cholesterol, but only partially prevented the high cholesterol diet-induced alterations in lipid profile. Quercetin prevented cholesterol-induced decreases in pancreatic ATP levels and mitochondrial bioenergetic dysfunction in Min6 cells, including decreases in mitochondrial membrane potentials and coupling efficiency in the mitochondrial respiration (basal and maximal oxygen consumption rate (OCR), ATP-linked OCR and reserve capacity).

Tridecanoin is anticonvulsant, antioxidant, and improves mitochondrial function.

The hypothesis that chronic feeding of the triglycerides of octanoate (trioctanoin) and decanoate (tridecanoin) in "a regular non-ketogenic diet" is anticonvulsant was tested and possible mechanisms of actions were subsequently investigated. Chronic feeding of 35E% of calories from tridecanoin, but not trioctanoin, was reproducibly anticonvulsant in two acute CD1 mouse seizure models. The levels of beta-hydroxybutyrate in plasma and brain were not significantly increased by either treatment relative to control diet.

Sulforaphane is anticonvulsant and improves mitochondrial function.

The nuclear factor erythroid 2-related factor 2 pathway (Nrf2) has been previously identified to protect the brain against various impacts. Here, we investigated the effect of the Nrf2 activator sulforaphane in various seizure models and hippocampal mitochondrial bioenergetics. We found that daily injections of sulforaphane for 5 days elevated the seizure thresholds to 6 Hz stimulation and fluorothyl-, but not pentylenetetrazole-induced tonic seizures and protected mice against pilocarpine-induced status epilepticus (SE).

Triheptanoin partially restores levels of tricarboxylic acid cycle intermediates in the mouse pilocarpine model of epilepsy.

Triheptanoin, the triglyceride of heptanoate, is anticonvulsant in various epilepsy models. It is thought to improve energy metabolism in the epileptic brain by re-filling the tricarboxylic acid (TCA) cycle with C4-intermediates (anaplerosis). Here, we injected mice with [1,2-(13) C]glucose 3.

Alterations of hippocampal glucose metabolism by even versus uneven medium chain triglycerides.

Medium chain triglycerides (MCTs) are used to treat neurologic disorders with metabolic impairments, including childhood epilepsy and early Alzheimer's disease. However, the metabolic effects of MCTs in the brain are still unclear. Here, we studied the effects of feeding even and uneven MCTs on brain glucose metabolism in the mouse.

Anticonvulsant screening of luteolin in four mouse seizure models.

Luteolin, a common plant polyphenolic flavonoid, has antioxidant, neuroprotective, anxiolytic and anti-inflammatory properties, which led us to hypothesize that luteolin is anticonvulsant. Here, we evaluated the effects of acute and chronic luteolin injection (i.p.