Influence of Fast, Body Weight and Diet on Serum Cholesterol, Triglycerides, and Phospholipids Concentrations in the Aging Rat

J, Boudet; Roullet, Jean Baptiste; Lacour, Bernard

doi:10.1055/s-2007-1010934

Cited by 8 publications

(6 citation statements)

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“…The present study assessed metabolic parameters, motor coordination and equilibrium, and spinal cord oxidative biomarkers in rats of different ages. The lack of changes in body weight, metabolic markers, and soleus muscle weight/body weight ratio with age was in line with previous studies (13,27,28). The slight decrease in blood glucose levels for old rats may be related to senescence; the median survival age for Wistar rats is 29–30 months (13).…”

Section: Discussionsupporting

confidence: 92%

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Age-related changes and effects of regular low-intensity exercise on gait, balance, and oxidative biomarkers in the spinal cord of Wistar rats

Silveira

Kroth

Santos

et al. 2019

Braz J Med Biol Res

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The present study aimed to analyze age-related changes to motor coordination, balance, spinal cord oxidative biomarkers in 3-, 6-, 18-, 24-, and 30-month-old rats. The effects of low-intensity exercise on these parameters were also analyzed in 6-, 18-, and 24-month-old rats. Body weight, blood glucose, total cholesterol, and high-density lipoprotein (HDL) cholesterol were assessed for all rats. The soleus muscle weight/body weight ratio was used to estimate skeletal muscle mass loss. Body weight increased until 24 months; only 30-month-old rats exhibited decreased blood glucose and increased total cholesterol and HDL cholesterol. The soleus muscle weight/body weight ratio increased until 18 months, followed by a small decrease in old rats. Exercise did not change any of these parameters. Stride length and step length increased from adult to middle age, but decreased at old age. Stride width increased while the sciatic functional index decreased in old rats. Performance in the balance beam test declined with age. While gait did not change, balance improved after exercise. Aging increased superoxide anion generation, hydrogen peroxide levels, total antioxidant capacity, and superoxide dismutase activity while total thiol decreased and lipid hydroperoxides did not change. Exercise did not significantly change this scenario. Thus, aging increased oxidative stress in the spinal cord, which may be associated with age-induced changes in gait and balance. Regular low-intensity exercise is a good alternative for improving age-induced changes in balance, while beneficial effects on gait and spinal cord oxidative biomarkers cannot be ruled out because of the small number of rats investigated (n=5 or 6/group).

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Section: Discussionsupporting

confidence: 92%

“…Rats were fed a standard diet throughout the entire experimental period, including prior to death. Fed aged rats did not experience changes in blood triglyceride levels (28). Thus, rats of the present study experienced changes that are commonly found during aging.…”

Section: Discussionmentioning

confidence: 99%

Age-related changes and effects of regular low-intensity exercise on gait, balance, and oxidative biomarkers in the spinal cord of Wistar rats

Silveira

Kroth

Santos

et al. 2019

Braz J Med Biol Res

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“…Analyses of plasma samples from humans and experimental animals indicate that cholesterol and triacylglycerol levels increase with aging (1)(2)(3). Aging increases total cholesterol and decreases phospholipids, leading to increased cholesterol-phospholipid molar ratios in hepatic mitochondria (4), brain (5), and cerebral synaptic membranes (6).…”

mentioning

confidence: 99%

Acetyl-l-carnitine supplementation restores decreased tissue carnitine levels and impaired lipid metabolism in aged rats

Tanaka

Sasaki

Fukui

et al. 2004

Journal of Lipid Research

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The effects of long-term carnitine supplementation on age-related changes in tissue carnitine levels and in lipid metabolism were investigated. The total carnitine levels in heart, skeletal muscle, cerebral cortex, and hippocampus were ‫ف‬ 20% less in aged rats (22 months old) than in young rats (6 months old). On the contrary, plasma carnitine levels were not affected by aging. Supplementation of acetyl-l -carnitine (ALCAR; 100 mg/kg body weight/day for 3 months) significantly increased tissue carnitine levels in aged rats but had little effect on tissue carnitine levels in young rats. Plasma lipoprotein analyses revealed that triacylglycerol levels in VLDL and cholesterol levels in LDL and in HDL were all significantly higher in aged rats than in young rats. ALCAR treatment decreased all lipoprotein fractions and consequently the levels of triacylglycerol and cholesterol. The reduction in plasma cholesterol contents in ALCAR-treated aged rats was attributable mainly to a decrease of cholesteryl esters rather than to a decrease of free cholesterol. Another remarkable effect of ALCAR was that it decreased the cholesterol content and cholesterol-phospholipid ratio in the brain tissues of aged rats. These results indicate that chronic ALCAR supplementation reverses the age-associated changes in lipid metabolism. Aging causes quantitative and compositional changes in body lipids. Analyses of plasma samples from humans and experimental animals indicate that cholesterol and triacylglycerol levels increase with aging (1-3). Aging increases total cholesterol and decreases phospholipids, leading to increased cholesterol-phospholipid molar ratios in hepatic mitochondria (4), brain (5), and cerebral synaptic membranes (6). These age-related changes in lipid composition in various tissues and organs are thought to account not only for the age-related accumulation of body fat, which is a risk factor for diabetes and atherosclerotic diseases, but also for age-related cellular hypofunction. Therefore, reversing age-related changes in lipid metabolism would help to maintain normal cellular function and prevent common diseases.Carnitine plays an essential role in transporting fatty acids into mitochondria, where they are oxidized to produce energy in tissues (7). Carnitine levels in cardiac and skeletal muscles, both of which are major storage sites of carnitine, appear to decrease with age (8-11). In plasma, however, it is unclear whether carnitine levels decease with age. Some studies have shown an increase in plasma carnitine levels with aging (12, 13), whereas others have found significant decreases in human (14) and rat (10). This inconsistency is a problem because plasma carnitine levels are often used as an index of body carnitine status. Concerning the age-related changes in carnitine levels in tissues and organs, cardiac and skeletal muscles have frequently been investigated (8-11), but other organs have not attracted much attention. One study reported a decrement of carnitine contents in the brain and a drast...

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“…Our study shows that TG accumulation in melanoma cells also increases the resistance to targeted therapy. These data suggest that targeting TG levels (27,28), which increase in older patients, could enhance response to targeted therapy in this population of patients with increased resistance to MAPK inhibition. Macrophages may be particularly susceptible to TGs, as it has been shown that during aging, the ability of macrophages to hydrolyze and utilize TGs is decreased, because of the loss of catecholamine-induced lipolysis.…”

Section: Cancermentioning

confidence: 81%

Changes in Aged Fibroblast Lipid Metabolism Induce Age-Dependent Melanoma Cell Resistance to Targeted Therapy via the Fatty Acid Transporter FATP2

et al. 2020

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Older patients with melanoma (>50 years old) have poorer prognoses and response rates to targeted therapy compared with young patients (<50 years old), which can be driven, in part, by the aged microenvironment. Here, we show that aged dermal fibroblasts increase the secretion of neutral lipids, especially ceramides. When melanoma cells are exposed to the aged fibroblast lipid secretome, or cocultured with aged fibroblasts, they increase the uptake of lipids via the fatty acid transporter FATP2, which is upregulated in melanoma cells in the aged microenvironment and known to play roles in lipid synthesis and accumulation. We show that blocking FATP2 in melanoma cells in an aged microenvironment inhibits their accumulation of lipids and disrupts their mitochondrial metabolism. Inhibiting FATP2 overcomes age-related resistance to BRAF/MEK inhibition in animal models, ablates tumor relapse, and significantly extends survival time in older animals. SIGNIFICANCE: These data show that melanoma cells take up lipids from aged fibroblasts, via FATP2, and use them to resist targeted therapy. The response to targeted therapy is altered in aged individuals because of the influences of the aged microenvironment, and these data suggest FATP2 as a target to overcome resistance. Montal and White, p. 1255. iNtRODUctiON Melanoma, like many other cancers, is a disease of aging, with incidence rising rapidly with age, and survival worsening even when controlling for tumor grade and stage (1). Mela-noma is the rarest yet deadliest form of skin cancer, with an estimated 6,850 deaths in the United States in the year 2020 alone (2). In contrast to other cancers, such as breast and lung cancers, where incidence has been steadily decreasing, melanoma incidence has been on the rise for the past 40 years and Cancer Research. See related commentary by

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Influence of Fast, Body Weight and Diet on Serum Cholesterol, Triglycerides, and Phospholipids Concentrations in the Aging Rat

Cited by 8 publications

References 0 publications

Age-related changes and effects of regular low-intensity exercise on gait, balance, and oxidative biomarkers in the spinal cord of Wistar rats

Age-related changes and effects of regular low-intensity exercise on gait, balance, and oxidative biomarkers in the spinal cord of Wistar rats

Acetyl-l-carnitine supplementation restores decreased tissue carnitine levels and impaired lipid metabolism in aged rats

Changes in Aged Fibroblast Lipid Metabolism Induce Age-Dependent Melanoma Cell Resistance to Targeted Therapy via the Fatty Acid Transporter FATP2

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