Sex differences in lipid metabolism and metabolic disease risk

2012 ◽  
Vol 90 (2) ◽  
pp. 124-141 ◽  
Author(s):  
Michael G. Sugiyama ◽  
Luis B. Agellon
Keyword(s):  
Metabolic Disease ◽  
Sex Differences ◽  
Body Fat ◽  
Molecular Mechanisms ◽  
Sex Chromosome ◽  
Disease Risk ◽  
Treatment Strategies ◽  
Metabolic Complications ◽  
Metabolic Disease Risk ◽  
Organ Systems

The ability of nutrients to regulate specific metabolic pathways is often overshadowed by their role in basic sustenance. Consequently, the mechanisms whereby these nutrients protect against or promote a variety of acquired metabolic syndromes remains poorly understood. Premenopausal women are generally protected from the adverse effects of obesity despite having a greater proportion of body fat than men. Menopause is often associated with a transformation in body fat morphology and a gradual increase in the susceptibility to metabolic complications, eventually reaching the point where women and men are at equal risk. These phenomena are not explained solely by changes in food preference or nutrient intake suggesting an important role for the sex hormones in regulating the metabolic fate of nutrients and protecting against metabolic disease pathophysiology. Here, we discuss how differences in the acquisition, trafficking, and subceullular metabolism of fats and other lipid soluble nutrients in major organ systems can create overt sex-specific phenotypes, modulate metabolic disease risk, and contribute to the rise in obesity in the modern sedentary climate. Identifying the molecular mechanisms underpinning sex differences in fat metabolism requires the unravelling of the interactions among sex chromosome effects, the hormonal milieu, and diet composition. Understanding the mechanisms that give rise to sex differences in metabolism will help to rationalize treatment strategies for the management of sex-specific metabolic disease risk factors.

scholarly journals New Insights into the Pathogenesis of Systemic Mastocytosis

2021 ◽  
Vol 22 (9) ◽  
pp. 4900
Author(s):  
Zhixiong Li
Keyword(s):  
Molecular Mechanisms ◽  
Kinase Inhibitor ◽  
Systemic Mastocytosis ◽  
Treatment Strategies ◽  
The United States ◽  
European Medicines Agency ◽  
Myeloid Neoplasm ◽  
Organ Systems ◽  
United States Food ◽  
Kit D816v

Mastocytosis is a type of myeloid neoplasm characterized by the clonal, neoplastic proliferation of morphologically and immunophenotypically abnormal mast cells that infiltrate one or more organ systems. Systemic mastocytosis (SM) is a more aggressive variant of mastocytosis with extracutaneous involvement, which might be associated with multi-organ dysfunction or failure and shortened survival. Over 80% of patients with SM carry the KIT D816V mutation. However, the KIT D816V mutation serves as a weak oncogene and appears to be a late event in the pathogenesis of mastocytosis. The management of SM is highly individualized and was largely palliative for patients without a targeted form of therapy in past decades. Targeted therapy with midostaurin, a multiple kinase inhibitor that inhibits KIT, has demonstrated efficacy in patients with advanced SM. This led to the recent approval of midostaurin by the United States Food and Drug Administration and European Medicines Agency. However, the overall survival of patients treated with midostaurin remains unsatisfactory. The identification of genetic and epigenetic alterations and understanding their interactions and the molecular mechanisms involved in mastocytosis is necessary to develop rationally targeted therapeutic strategies. This review briefly summarizes recent developments in the understanding of SM pathogenesis and potential treatment strategies for patients with SM.

Red Wine High-Molecular-Weight Polyphenolic Complex: An Emerging Modulator of Human Metabolic Disease Risk and Gut Microbiota

2021 ◽  
Vol 69 (37) ◽  
pp. 10907-10919
Author(s):  
Hao Suo ◽  
Mohammad Rezaul Islam Shishir ◽  
Jianbo Xiao ◽  
Mingfu Wang ◽  
Feng Chen ◽  
...  
Keyword(s):  
Metabolic Disease ◽  
Molecular Weight ◽  
Gut Microbiota ◽  
High Molecular Weight ◽  
Red Wine ◽  
Disease Risk ◽  
Metabolic Disease Risk

scholarly journals CBMT-45. SEX-SPECIFIC METABOLIC ADAPTIONS IN GLIOBLASTOMA

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi42-vi43
Author(s):  
Jasmin Sponagel ◽  
Shanshan Zhang ◽  
Prakash Chinnaiyan ◽  
Joshua Rubin ◽  
Joseph Ippolito
Keyword(s):  
Sex Differences ◽  
Sexual Dimorphism ◽  
Molecular Mechanisms ◽  
Treatment Strategies ◽  
Tca Cycle ◽  
Metabolic Reprogramming ◽  
Mitochondrial Activity ◽  
Male And Female ◽  
Glutamine Deprivation ◽  
Novel Treatment Strategies

Abstract Glioblastoma (GBM) is the most common and aggressive brain tumor in adults. GBM occurs more commonly in males, but female patients survive significantly longer. Understanding the molecular mechanisms that underlie those sex differences could support novel treatment strategies. In this regard, we found that male and female GBM patient samples differ in their metabolite abundance and that male patients exhibit a significantly higher abundance of TCA cycle metabolites. We confirmed those findings in a murine model of GBM, which has previously yielded important insights into sexual dimorphism in GBM. Strikingly, sex differences in TCA cycle flux were entirely driven by glutamine flux, not glucose flux, suggesting a sex-specific role for glutamine in GBM. Metabolic manipulation through glutamine deprivation resulted in a greater growth inhibition in male GBM cells. Glutamine itself can be utilized for anabolic reactions or it can be converted to glutamate by glutaminase. Only male GBM cells were sensitive to pharmacological glutaminase inhibition with BPTES or CB-839, suggesting that male GBM cells are glutamate dependent while female GBM cells are not. Concordantly, we found significantly higher glutaminase levels in male GBM cells. Furthermore, we found that numerous metabolites (including NADH, ATP, and glutathione) involved in cellular processes downstream of glutamate were more abundant in male GBM cells. In contrast, female GBM cells were resistant to low glutamine conditions and glutaminase inhibitors unless glutamine-synthase activity was disrupted, suggesting that glutamine synthesis might play a more prominent role in female GBM. Together, these data indicate that male and female GBM differ in their metabolic adaptions. Male GBM utilize glutamate to fuel the TCA cycle and mitochondrial activity while female GBM synthesize and utilize glutamine itself. This sexual dimorphism in metabolic reprogramming reveals novel sex specific metabolic targets for GBM and underlines the importance of considering sex in metabolic targeting approaches.

scholarly journals Lactational programming of glucose homeostasis: a window of opportunity

Reproduction ◽  
2018 ◽  
Vol 156 (2) ◽  
pp. R23-R42 ◽  
Author(s):  
Lindsay Ellsworth ◽  
Emma Harman ◽  
Vasantha Padmanabhan ◽  
Brigid Gregg
Keyword(s):  
Metabolic Disease ◽  
Glucose Homeostasis ◽  
Critical Period ◽  
Disease Risk ◽  
Milk Composition ◽  
Lactation Period ◽  
Cellular Functions ◽  
Environmental Endocrine Disruptors ◽  
Metabolic Disease Risk ◽  
Underlying Mechanisms

The window of lactation is a critical period during which nutritional and environmental exposures impact lifelong metabolic disease risk. Significant organ and tissue development, organ expansion and maturation of cellular functions occur during the lactation period, making this a vulnerable time during which transient insults can have lasting effects. This review will cover current literature on factors influencing lactational programming such as milk composition, maternal health status and environmental endocrine disruptors. The underlying mechanisms that have the potential to contribute to lactational programming of glucose homeostasis will also be addressed, as well as potential interventions to reduce offspring metabolic disease risk.

scholarly journals Cardio-metabolic disease risk factors among South Asian labour migrants to the Middle East: a scoping review and policy analysis

2019 ◽  
Vol 15 (1) ◽  
Author(s):  
Shiva Raj Mishra ◽  
Saruna Ghimire ◽  
Chandni Joshi ◽  
Bishal Gyawali ◽  
Archana Shrestha ◽  
...  
Keyword(s):  
Risk Factors ◽  
Metabolic Disease ◽  
Middle East ◽  
Policy Analysis ◽  
South Asian ◽  
Scoping Review ◽  
Disease Risk ◽  
Metabolic Disease Risk

scholarly journals Weight Loss Efficacy of 4-Hour Versus 6-Hour Time Restricted Feeding in Adults with Obesity

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 584-584
Author(s):  
Sofia Cienfuegos ◽  
Kelsey Gabel ◽  
Faiza Kalam ◽  
Mark Ezpeleta ◽  
Vasiliki Pavlou ◽  
...  
Keyword(s):  
Risk Factors ◽  
Metabolic Disease ◽  
Insulin Resistance ◽  
Blood Pressure ◽  
Weight Loss ◽  
Body Weight ◽  
Fat Mass ◽  
Disease Risk ◽  
Metabolic Disease Risk ◽  
Ad Libitum

Abstract Objectives This study was undertaken to compare the effects of 4-h TRF to that of 6-h TRF on body weight, body composition, and metabolic disease risk factors in adults with obesity. We hypothesized that 4-h TRF would produce the greatest decreases in body weight, fat mass, blood pressure, and insulin resistance, compared to 6-h TRF. Methods Adults with obesity (n = 49) were randomized to 1 of 3 interventions for 8 weeks: 4-h TRF (ad libitum eating between 3:00 to 7:00 pm, water fasting between 7:00 to 3:00 pm); 6-h TRF (ad libitum eating between 1:00 to 7:00 pm, water fasting between 7:00 to 1:00 pm); or control (ad libitum food intake with no timing restrictions). Results Body weight decreased similarly in the 4-h TRF group (–3.3 ± 0.5%) and 6-h TRF group (–2.6 ± 0.5%) relative to controls over 8 weeks (P < 0.001). Fat mass, blood pressure and insulin sensitivity also decreased in the 4-h TRF and 6-h TRF groups versus controls. LDL cholesterol, HDL cholesterol, triglycerides, fasting glucose, and HbA1c were not significantly different from controls after 8 weeks. Conclusions This is the first trial to examine the effects of 4-h vs. 6-h TRF on body weight and metabolic disease risk factors. We show here that 8 weeks of 4-h and 6-h TRF decreases body weight by ∼3–4% relative to controls. We also demonstrate that this fasting regimen produces significant reductions in blood pressure, fat mass, insulin and insulin resistance. These preliminary data offer promise for the use of 4-h and 6-h TRF as a weight loss techniques in adults with obesity, but larger, longer-term trials are needed to confirm these findings. Funding Sources Department of Kinesiology and Nutrition, University of Illinois Chicago

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