Acid sphingomyelinase inhibitors, imipramine and zoledronic acid, increase skeletal muscle tissue sensitivity to insulin action at old age.

Malfunction of skeletal muscles and dysregulated turnover of sphingolipids in the insulin responsive tissues have been determined at old age. Present article investigates the role of acid sphingomyelinase (SMase)-dependent ceramide accumulation in reduction of the skeletal muscle sensitivity to insulin action at old age. The 3-, 12- and 24-month-old Wistar male rats were used in the experiments.

Role of acid sphingomyelinase in the age-dependent dysregulation of sphingolipids turnover in the tissues of rats.

Old age-associated pathologies usually coincide with altered sphingolipid metabolism. In the present article, the role of acid sphingomyelinase (ASMase) in the age-dependent changes of sphingomyelin (SM) and ceramide contents in the tissues has been investigated by means of ASMase inhibitors, imipramine and zoledronic acid. It has been determined that ceramide content and ceramide/SM ratio increased, while SM level decreased in the heart, liver, blood serum and skeletal muscles of 24-month old rats in contrast to 3-month old animals.

Effects of inhibitors of key enzymes of sphingolipid metabolism on insulin-induced glucose uptake and glycogen synthesis in liver cells of old rats.

Sphingolipids play an important role in the development of insulin resistance. Ceramides are the most potent inhibitors of insulin signal transduction. Ceramides are generated in response to stress stimuli and in old age.

Long-term food restriction prevents aging-associated sphingolipid turnover dysregulation in the brain.

Abnormalities of sphingolipid turnover in the brain during normal aging and age-related neurological disorders were associated with the neurons loss and cognitive malfunction. Calorie restriction (CR) prevented age-related deficits in hippocampal long-term potentiation and improved cognitive function at old age. In the paper we investigated the ceramide and sphingomyelin (SM) levels in the brain regions, which are critical for learning and memory of 3- and 24-month-old rats, as well as the correction of sphingolipid turnover in the brain of old rats, by means of the CR diet and modulators of SM turnover.

Vitamin E prevents the age-dependent and palmitate-induced disturbances of sphingolipid turnover in liver cells.

Sphingolipid turnover has been shown to be activated at old age and in response to various stress stimuli including oxidative stress. Reduction of vitamin E content in the liver under the pro-oxidant action is associated with enhanced sphingolipid turnover and ceramide accumulation in hepatocytes. In the present paper, the correction of sphingolipid metabolism in the liver cells of old rats and in the palmitate-treated young hepatocytes using α-tocopherol has been investigated.

Effects of long-term fish oil-enriched diet on the sphingolipid metabolism in brain of old rats.

An increase of the neutral sphingomyelinase (SMase) activity in the animal brain at old age is associated with a higher expression of the inflammatory marker, interleukin-1beta and a cognitive decline. Dietary n-3 polyunsaturated fatty acids (n-3 PUFA) are found to exhibit anti-inflammatory effects and normalize the age- or dementia-related cognitive function decline. In the paper we investigate the ceramide, sphingomyelin (SM) and phosphatidylserine (PS) levels in the hippocampus of 3-month-old-32-month-old rats as well as the correction of sphingolipid turnover in the brain of old rats by means of the dietetic fish oil and PS.

Calorie restricted diet induces alternative pathways of lipid metabolism for support of proliferative processes in regenerating liver.

This study deals with quality and quantity lipid composition of blood serum and liver, DNA synthesis activity (incorporation of H3-thymidine) in liver in 24 h after partial hepatectomy (PH) in 22-month-old Wistar rats, maintained for 21 months on calorie restricted diet (CRD) and on standard diet ad libitum (SD). The contain of lipids in blood serum and activity of RA-label incorporation (14C-Na-acetate) in serum lipids in 24 h after PH were the same in CRD-fed and SD-fed animals. Quantitative and qualitative composition of lipids in microsomes of regenerating liver also was the same for both groups of rats.

Effects of flavonoids on sphingolipid turnover in the toxin-damaged liver and liver cells.

Background: The ceramide generation is an early event in the apoptotic response to numerous stimuli including the oxidative stress and ceramide analogs mimic the stress effect and induce apoptosis. Flavonoids of German chamomile are reported to exhibit the hepatoprotective effect. Flavonoids affect sphingolipid metabolism and reduce the elevated ceramide level in the aged liver.

Effects of Chamomilla recutita flavonoids on age-related liver sphingolipid turnover in rats.

The increased sphingolipid turnover in the liver is associated with elevation of free radical production and state of chronic inflammation at old age. Plant polyphenols are reported to exhibit antioxidant and anti-inflammatory effects. In the present paper, the lipids contents and ceramide production in the liver and hepatocytes as well as the correction of sphingolipid metabolism at old age using the mixture of Chamomilla recutita flavonoids (chamiloflan) or apigenin-7-glucoside or luteolin-7-glucoside alone have been investigated.

Long- and short-term effects of thyroxine on sphingolipid metabolism in rat liver.

Background: Thyroid hormones are well known as modulators of signal transduction. Early experiments showed that sustained elevation of diacylglycerol (DAG) and ceramide levels in liver cells of hypothyroid rats is an essential prerequisite for disturbances in agonist responsiveness of hepatocytes. In this paper the effects of thyroxine (L-T(4)) on sphingolipid mass, synthesis, and degradation are investigated.