Calorie restriction potentiates epigallocatechin-3-gallate-mediated Nrf2 activation in hepatocytes of aged rats

Objective:To explore the combinatorial effect of epigallocatechin-3-gallate(EGCG)and calorie restriction on activation of nuclear factor erythroid 2-related factor 2(Nrf2),a transcription factor involved in the antioxidant defense system of aged rats.Methods:Aged male Wistar rats were calorie-restricted and treated with EGCG orally for 45 days.The initial body weight of aged rats was recorded,and the final body weight was measured at the end of the experimental period.Serum lipid and lipoprotein status,oxidative stress markers such as free radicals and malondialdehyde levels,and reduced glutathione were assessed.In addition,RT-PCR and Western blotting analyses were performed.Results:Calorie restriction potentiated the effect of EGCG on enhancing antioxidant status,improving the levels of serum lipid and lipoproteins,upregulating Nrf2 and Bcl2,and downregulating Keap1,cullin3,Bax and cytochrome c in aged rats.Conclusions:Calorie restriction can promote EGCG-mediated Nrf2 activation in aged rats.This preliminary finding paves the way for a combinatory approach to replenishing the antioxidant status during aging,thereby reducing the risk for age-associated degenerative diseases.

Changes Induced by Physical Activity, Weight Loss and Calorie Restriction in Body Composition, Lipoproteins and Functional Capacity in Obese Congolese Women

Background. The effects of physical exercises combined with a low-calorie diet on weight loss, body composition, lipoproteins profile, and physical fitness had been well described. However, Central Africa’s studies investigating these kinds of diets and exercise regimens are lacking. Objective. To investigate the effects of adding 14-weeks exercises to a hypocaloric diet on changes in body composition, lipoproteins concentrations, and physical capacities in obese Congolese women. Population and Methods. In total, 34 obese women aged 30 - 39 years (mean age: 33.7 ± 2.4 years) assigned to 14-weeks training program and low energy ketogenic diet. Body composition was assessed using classic methods and impedancemetry. Fasting plasma glucose (FPG) and fasting serum insulin were assessing using enzymatic colorimetric and radioim-munoradiometric methods. HOMA-IR and lipoproteins concentrations were assessed using standardized laboratory methods. VO2peak was measured on a treadmill during a progressive exercise test. Speed, cadence and stride length were measured along the 10-m level walkway. Muscular endurance was measured using the tests of sit-up and inflections-extensions of elbows. All the variables of the study were assessed at the beginning, in the 7-weeks, and in the 14-weeks of training methods. Results. Declines in body weight (16%), percent fat (12.1%), fat weight (26.4%), abdominal fat (34.2%), and waist circumference (10.4%) were found. A significant decrease in FPG (13%), fasting serum insulin (60.9%), HOMA-IR (64.7%), total cholesterol (12.2%), LDL-cholesterol (20.3%), triglycerides (92.8%), and VLDL-triglycerides (17.5%) was shown. In contrast, significant increase in HDL-cholesterol (27.13%) was found. The peak oxygen consumption VO2peak relative to body weight improved more in the 14-weeks training program (13.4%). Obese women exhibited higher values in the 14-weeks training program for speed gait (16.5%), cadence (9.1%), and stride length (15.7%) during normal walk and rapid walk. Weight loss combined with a low-calorie diet and 14-weeks training program improved significantly muscular endurance capacities. Conclusion. Exercise added to hypocaloric diet leads to decreases in body composition, to improve in insulin sensitivity, to enhancement of VO2peak and functional fitness. This may be helpful for the treatment of the metabolic complications of abdominal obesity.

The ATP Level in the mPFC Mediates the Antidepressant Effect of Calorie Restriction

Food deprivation can rescue obesity and overweight-induced mood disorders,and promote mood performance in normal subjects.Animal studies and clinical research have revealed the antidepressant-like effect of calorie restriction,but little is known about the mechanism of calorie restriction-induced mood modification.Previous studies have found that astrocytes modulate depressive-like behaviors.Inositol 1,4,5-trisphosphate receptor type 2(IP3R2)is the predominant isoform in mediating astrocyte Ca2+signals and its genetic knockout mice are widely used to study astrocyte function in vivo.In this study,we showed that deletion of IP3R2 blocked the antidepressant-like effect induced by calorie restriction.In vivo microdialysis experiments demonstrated that calorie restriction induced an increase in ATP level in the medial prefrontal cortex(mPFC)in naïve mice but this effect disappeared in IP3R2-knockout mice,suggesting a role of astrocytic ATP in the calorie restriction-induced antidepressant effect.Further experiments showed that systemic administration and local infusion of ATP into the mPFC induced an antidepressant effect,whereas decreasing ATP by Apyrase in the mPFC blocked calorie restriction-induced antidepressant regulation.Together,these findings support a role for astrocytic ATP in the antidepressant–like effect caused by calorie restriction.

Age-related driving mechanisms of retinal diseases and neuroprotection by transcription factor EB-targeted therapy

Retinal aging has been recognized as a significant risk factor for various retinal disorders,including diabetic retinopathy,age-related macular degeneration,and glaucoma,following a growing understanding of the molecular underpinnings of their development.This comprehensive review explores the mechanisms of retinal aging and investigates potential neuroprotective approaches,focusing on the activation of transcription factor EB.Recent meta-analyses have demonstrated promising outcomes of transcription factor EB-targeted strategies,such as exercise,calorie restriction,rapamycin,and metformin,in patients and animal models of these common retinal diseases.The review critically assesses the role of transcription factor EB in retinal biology during aging,its neuroprotective effects,and its therapeutic potential for retinal disorders.The impact of transcription factor EB on retinal aging is cell-specific,influencing metabolic reprogramming and energy homeostasis in retinal neurons through the regulation of mitochondrial quality control and nutrient-sensing pathways.In vascular endothelial cells,transcription factor EB controls important processes,including endothelial cell proliferation,endothelial tube formation,and nitric oxide levels,thereby influencing the inner blood-retinal barrier,angiogenesis,and retinal microvasculature.Additionally,transcription factor EB affects vascular smooth muscle cells,inhibiting vascular calcification and atherogenesis.In retinal pigment epithelial cells,transcription factor EB modulates functions such as autophagy,lysosomal dynamics,and clearance of the aging pigment lipofuscin,thereby promoting photoreceptor survival and regulating vascular endothelial growth factor A expression involved in neovascularization.These cell-specific functions of transcription factor EB significantly impact retinal aging mechanisms encompassing proteostasis,neuronal synapse plasticity,energy metabolism,microvasculature,and inflammation,ultimately offering protection against retinal aging and diseases.The review emphasizes transcription factor EB as a potential therapeutic target for retinal diseases.Therefore,it is imperative to obtain well-controlled direct experimental evidence to confirm the efficacy of transcription factor EB modulation in retinal diseases while minimizing its risk of adverse effects.

Hysteresis of White Adipose Tissue

Objective: This study was performed to analyze the modifications within adipose tissue during calorie restriction and more specifically to state whether hysteresis occurs during fat mass reduction. Method: Rats male Wistar increased their body weight by 130 g under control conditions and were then submitted to a calorie restriction (CR) at 30% or 60% of control. Experiment has been stopped when the body weight of the group CR60% returned back to its initial value. Samples of retroperitoneal adipose tissue were collected by biopsies along the study. Adipose cell size was analyzed using multisizer IV (Beckman Coulter) to determine the size distribution curves during natural growth and after calorie restriction. Results: After CR60%, body weights and adipose tissue masses were similar to the ones at the beginning of the experiment. Adipose cell size distribution curve was shifted to the left compared to the one of initial control. Adipose cell sizes were significantly lower after CR60% than those of control at the beginning of the experiment. Conclusions: These results state for the first time that hysteresis occurs in white adipose tissue after calorie restriction. The composition of adipose tissue after calorie restriction was significantly different than the one of initial control. After significant weight loss, organisms must be considered as different from the initial controls, they are most likely governed by different regulations which will have to be identified.

Regulation of the urea cycle by CPS1 O-GlcNAcylation in response to dietary restriction and aging

O-linked N-acetyl-glucosamine glycosylation(O-GlcNAcylation)of intracellular proteins is a dynamic process broadly implicated in age-related disease,yet it remains uncharacterized whether and how O-GlcNAcylation contributes to the natural aging process.O-GlcNAc transferase(OGT)and the opposing enzyme O-GlcNAcase(OGA)control this nutrient-sensing protein modification in cells.Here,we show that global O-GlcNAc levels are increased in multiple tissues of aged mice.In aged liver,carbamoyl phosphate synthetase 1(CPS1)is among the most heavilyO-GlcNAcylated proteins.CPS1O-GlcNAcylation is reversed by calorie restriction and is sensitive to genetic and pharmacological manipulations of theO-GlcNAc pathway.High glucose stimulates CPS1O-GlcNAcylation and inhibits CPS1 activity.Liver-specific deletion of OGT potentiates CPS1 activity and renders CPS1 irresponsive to further stimulation by a prolonged fasting.Our results identify CPS1 O-GlcNAcylation as a key nutrient-sensing regulatory step in the urea cycle during aging and dietary restriction,implying a role for mitochondrial O-GlcNAcylation in nutritional regulation of longevity.