Combined Effect of Gender and Caloric Restriction on Liver Proteomic Expression Profile

Valle, Adamo; Silvestri, Elena; Moreno, María; Oliver, Jordi; Roca, Pilar; Goglia, Fernando

doi:10.1021/pr800086t

Cited by 17 publications

(11 citation statements)

References 77 publications

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“…It is thus not surprising that invertebrate data (Drosophila) suggest that age-related iron accumulation is proportional to the rate of aging (Massie et al, 1985) and inhibition of iron absorption prolongs lifespan (Massie et al, 1993). Similarly, human gender differences in longevity have been proposed to relate to reproduction-related iron losses in women (Sullivan, 1989) and life-extending effects of calorie restriction have been associated with reduced dietary iron uptake and lowered iron deposits in tissue (Cook and Yu, 1998;Kastman et al, 2010;Valle et al, 2008;Xu et al, 2008).…”

Section: Discussionmentioning

confidence: 99%

Gender and Iron Genes May Modify Associations Between Brain Iron and Memory in Healthy Aging

Bartzokis

Tingus

et al. 2011

Neuropsychopharmacol

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Brain iron increases with age and is abnormally elevated early in the disease process in several neurodegenerative disorders that impact memory including Alzheimer's disease (AD). Higher brain iron levels are associated with male gender and presence of highly prevalent allelic variants in genes encoding for iron metabolism proteins (hemochromatosis H63D (HFE H63D) and transferrin C2 (TfC2)). In this study, we examined whether in healthy older individuals memory performance is associated with increased brain iron, and whether gender and gene variant carrier (IRON + ) vs noncarrier (IRONÀ) status (for HFE H63D/TfC2) modify the associations. Tissue iron deposited in ferritin molecules can be measured in vivo with magnetic resonance imaging utilizing the field-dependent relaxation rate increase (FDRI) method. FDRI was assessed in hippocampus, basal ganglia, and white matter, and IRON + vs IRONÀ status was determined in a cohort of 63 healthy older individuals. Three cognitive domains were assessed: verbal memory (delayed recall), working memory/attention, and processing speed. Independent of gene status, worse verbal-memory performance was associated with higher hippocampal iron in men (r ¼ À0.50, p ¼ 0.003) but not in women. Independent of gender, worse verbal working memory performance was associated with higher basal ganglia iron in IRONÀ group (r ¼ À0.49, p ¼ 0.005) but not in the IRON + group. Between-group interactions (p ¼ 0.006) were noted for both of these associations. No significant associations with white matter or processing speed were observed. The results suggest that in specific subgroups of healthy older individuals, higher accumulations of iron in vulnerable gray matter regions may adversely impact memory functions and could represent a risk factor for accelerated cognitive decline. Combining genetic and MRI biomarkers may provide opportunities to design primary prevention clinical trials that target high-risk groups.

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Section: Discussionmentioning

confidence: 99%

Gender and Iron Genes May Modify Associations Between Brain Iron and Memory in Healthy Aging

Bartzokis

Tingus

et al. 2011

Neuropsychopharmacol

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“…The overall metabolism of fuel molecules displays sex differences, and in this context many hepatic proteins are expressed in a sexually dimorphic fashion (13,17,39). With relevance to hepatic glycerol metabolism, the expression of AQP9 protein is ϳ20% higher in male than in female rats in the postprandial state (26).…”

Section: Discussionmentioning

confidence: 99%

Estrogen prevents increased hepatic aquaporin-9 expression and glycerol uptake during starvation

Lebeck

Gena

O’Neill

et al. 2012

American Journal of Physiology-Gastrointestinal and Liver Physi

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In starvation, glycerol is released from adipose tissue and serves as an important precursor for hepatic gluconeogenesis. By unknown sex-specific mechanisms, women suppress the endogenous glucose production better than men and respond to metabolic stress with higher plasma glycerol levels. Hepatic glycerol uptake is facilitated by aquaporin-9 (AQP9), a broad-selectivity neutral solute channel, and represents an insulin-regulated step in supplying gluconeogenesis with glycerol. In the present study, hepatic AQP9 abundance was increased 2.6-fold in starved male rats as assessed by immunoblotting and immunohistochemistry. By contrast, starvation had no significant effect on hepatic AQP9 expression in female rats. Coordinately, plasma glycerol levels remained unchanged with starvation in male rats, whereas it was increased in female rats. The different responses to starvation were paralleled by higher glycerol permeability in basolateral hepatocyte membranes from starved male rats compared with starved females. Ovariectomy led to a starvation-response pattern identical to that observed in male rats with increased hepatic AQP9 expression and unchanged plasma glycerol levels. In cultured hepatocytes, 17β-estradiol and the selective estrogen receptor α-agonist, propyl pyrazole triol, caused a decrease in AQP9 expression. Our results support that a sex-specific regulation of the hepatic glycerol channel AQP9 during starvation contributes to the higher plasma glycerol levels observed in women during fasting and possibly results in a lower cytosolic availability of glycerol. Furthermore, the sexual dimorphism in the hepatic handling of glycerol during starvation might be explained by 17β-estradiol preventing the starvation-induced increase in hepatic AQP9 abundance.

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“…They showed that glycolytic enzymes were less abundant in females in non-exercised murine skeletal muscle. Valle and colleagues [27] analyzed the combined effect of gender and caloric restriction on the protein expression profile in rat liver, and identified 31 sexually dimorphic (15 femaleand 16 male-dominant) proteins. However, differentially expressed proteins were interpreted in relation to longevity rather than obesity.…”

Section: Introductionmentioning

confidence: 99%

Gender Dimorphism in Skeletal Muscle Proteome Between Lean and Diet-induced Obese Rats

Choi

et al. 2011

Cell Physiol Biochem

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Background: Although it has been believed for a long time that gender differences in physiology and metabolism were not relevant beyond the reproductive system, new research has indicated that sexual dimorphism may be more prevalent than previously believed. Therefore, the goal of this study was to develop a global view of the changes in gender-dependent protein abundance in two different types of skeletal muscles (soleus and gastrocnemius) of lean and high fat diet (HFD)-induced obese rats. Methods: To examine differential expression of proteins between gender and diet, we performed differential proteome analysis of skeletal muscle from lean and obese rats of both genders fed a HFD using 2-DE combined with MALDI-TOF-MS. Results: Our gender-specific proteome comparison showed that male and female rats displayed different patterns of proteome regulation including proteins involved in muscle contraction, carbohydrate and lipid metabolism, oxidative phosphorylation, as well as detoxification and antioxidant defenses. Conclusions: most of the candidate proteins identified herein by differential proteomics were previously unrecognized in gender dimorphism of skeletal muscle. Our data can serve as the basis for specific evidence-based interventions allowing for the prevention and treatment of obesity by matching the different needs of women and men such as the development of gender-based medicine.

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Combined Effect of Gender and Caloric Restriction on Liver Proteomic Expression Profile

Cited by 17 publications

References 77 publications

Gender and Iron Genes May Modify Associations Between Brain Iron and Memory in Healthy Aging

Gender and Iron Genes May Modify Associations Between Brain Iron and Memory in Healthy Aging

Estrogen prevents increased hepatic aquaporin-9 expression and glycerol uptake during starvation

Gender Dimorphism in Skeletal Muscle Proteome Between Lean and Diet-induced Obese Rats

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