Sex Differences In Lipid Metabolism Research Articles

Sex Differences in Energy Metabolism: A Female-Oriented Discussion.

The purpose of this review is to delineate aspects of energy metabolism at rest and during exercise that may be subject to sex differences and the potential underlying mechanisms involved. It focuses on distinct aspects of female physiology with an oriented discussion following the reproductive life stages of healthy, eumenorrheic females, including premenopausal time frames, pregnancy, perimenopause, and menopause. Finally, this review aims to address methodological challenges surrounding sexual dimorphism in energy metabolism investigations and confounding factors in this field. During resting conditions, females tend to have higher rates of non-oxidative free fatty acid clearance, which could contribute to lower respiratory exchange ratio measures. At the same time, carbohydrate energy metabolism findings are mixed. In general, females favor lipid energy metabolism during moderate-intensity exercise, while men favor carbohydrate energy metabolism. Factors such as age, dietary intake, genetics, and methodological decisions confound study findings, including properly identifying and reporting the menstrual cycle phase when female subjects are eumenorrheic. Pregnancy presents a unique shift in physiological systems, including energy metabolism, which can be observed at rest and during exercise. Changes in body composition and hormonal levels during the post-menopausal period directly impact energy metabolism, specifically lipid metabolism. This change in physiological state factors into the evidence showing a reduction in our understanding of sex differences in lipid metabolism during exercise in older adults. This review reveals a need for a focused understanding of female energy metabolism that could help exercise and nutrition professionals optimize female health and performance across the lifespan.

Sex differences in lipid metabolism may explain disparities in cardiometabolic disease prevalence with sleep apnoea.

Sex differences in lipid metabolism may explain disparities in cardiometabolic disease prevalence with sleep apnoea.

Sexual Dimorphism in Lipid Metabolism and Gut Microbiota in Mice Fed a High-Fat Diet.

The gut microbiome plays an essential role in regulating lipid metabolism. However, little is known about how gut microbiome modulates sex differences in lipid metabolism. The present study aims to determine whether gut microbiota modulates sexual dimorphism of lipid metabolism in mice fed a high-fat diet (HFD). Conventional and germ-free male and female mice were fed an HFD for four weeks, and lipid absorption, plasma lipid profiles, and apolipoprotein levels were then evaluated. The gut microbiota was analyzed by 16S rRNA gene sequencing. After 4-week HFD consumption, the females exhibited less body weight gain and body fat composition and significantly lower triglyceride levels in very-low-density lipoprotein (VLDL) and cholesterol levels in high-density lipoprotein (HDL) compared to male mice. The fecal microbiota analysis revealed that the male mice were associated with reduced gut microbial diversity. The female mice had considerably different microbiota composition compared to males, e.g., enriched growth of beneficial microbes (e.g., Akkermansia) and depleted growth of Adlercreutzia and Enterococcus. Correlation analyses suggested that the different compositions of the gut microbiota were associated with sexual dimorphism in body weight, fat mass, and lipid metabolism in mice fed an HFD. Our findings demonstrated significant sex differences in lipid metabolism and the microbiota composition at baseline (during LFD), along with sex-dependent responses to HFD. A comprehensive understanding of sexual dimorphism in lipid metabolism modulated by microbiota will help to develop more sex-specific effective treatment options for dyslipidemia and metabolic disorders in females.

Male and female mice display sex differences in lipid metabolism: Long-term atorvastatin or rosuvastatin administration impaired locomotive activity and cardiac relaxation in both sexes

Introduction: Statins are HMG-CoA reductase inhibitors and are among the most used drugs. Statins are prescribed to reduce low density lipoprotein-Cholesterol (LDL-C) levels for the prevention and treatment of cardiovascular disease. HMG-CoA reductase is ubiquitously expressed in the ER-membrane. The most common adverse effect are statin-associated muscle symptoms (SAMS) ranging from muscle weakness, pain, cramps, exercise intolerance to rare cases of rhabdomyolysis. Women are more likely to report SAMS, but the mechanisms of sex differences in statin adverse events are unknown. Effects on mitochondrial pathways play an important role in statin-induced myopathy. We previously showed that the lipophilic atorvastatin (Ator), but not the hydrophilic pravastatin, increased sudden death in cardiomyopathic mice due to mitochondrial alteration. Because hydrophilic statins are thought to be better tolerated due to less intracellular access, we hypothesized that the hydrophilic rosuvastatin (Rosu) may lead to fewer statin adverse effects when compared to Ator. Methods: 8-week-old male (M) and female (F) C57BL6J mice received either Ator (5mg/kg), Rosu (5mg/kg), or vehicle (Veh, 10% EtOH in water,) by daily oral gavage (6 groups, M+Ator, F+Ator, M+Rosu, F+Rosu, M+Veh, and F+Veh, n= 9-12 each). A lipid panel, liver enzymes, and creatine kinase (CK) were analyzed 4-month(m) post statin administration (n=8 each). Voluntary home cage activity was assessed 4-months (m) and echocardiography performed at 10-m after treatment start. Results: Prior to treatment M+Veh mice presented higher total-C and high-density lipoprotein (HDL)-C serum levels than F+ Veh mice (total- C mg/dl, Mean ± SEM; M+Veh 131.4 ± 7.4, F+Veh 90.5 ± 4.8, M+Veh vs F+Veh, * p<0.0004, and HDL-C mg/dl, Mean ± SEM; M+Veh 82.8 ± 3.3, F+Veh 58.6 ± 3.4, M+Veh vs F+Veh, * p<0.0002). Ator and Rosu administration did not alter CK levels but reduced voluntary total distance moved in M+Ator, M+Rosu, F+Ator, and F+Rosu mice, when compared to M+Veh and F+Veh. After 10m-long daily statin or vehicle administration, echocardiography revealed that M+Ator, M+Rosu, F+Ator, and F+Rosu presented preserved systolic ejection fraction (%EF) while tissue Doppler analysis detected decreased E’/A’ ratios (M+Veh 2.38±0.15, M+Ator 1.47±0.21, M+Rosu 1.5±0.18, F+Veh 1.99±0.15, F+Ator 1.11± 0.17, F+Rosu 0.97± 0.14, statin vs statin per sex non-significant, statin vs Veh per sex p < 0.004, n=9-12 each). Conclusion: Long-term Ator and Rosu administration reduced voluntary cage activity and induced diastolic dysfunction with preserved systolic function in male and female mice to a similar degree. Despite its hydrophilicity, the greater LDL-C lowering efficacy and longer half-live of Rosu may attribute to these findings. In male and female mice, we show for first time that long-term Ator and Rosu administration induced physiological alterations found in heart failure with preserved ejection fraction. Veterans Medical Research Foundation/San Diego Pilot Project Award, Zemljic-Harpf (PI), UC San Diego ANES Research Seed Award, Zemljic-Harpf (PI) This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Lipidome- and Genome-Wide Study to Understand Sex Differences in Circulatory Lipids.

Background Despite well-recognized differences in the atherosclerotic cardiovascular disease risk between men and women, sex differences in risk factors and sex-specific mechanisms in the pathophysiology of atherosclerotic cardiovascular disease remain poorly understood. Lipid metabolism plays a central role in the development of atherosclerotic cardiovascular disease. Understanding sex differences in lipids and their genetic determinants could provide mechanistic insights into sex differences in atherosclerotic cardiovascular disease and aid in precise risk assessment. Herein, we examined sex differences in plasma lipidome and heterogeneity in genetic influences on lipidome in men and women through sex-stratified genome-wide association analyses. Methods and Results We used data consisting of 179 lipid species measured by shotgun lipidomics in 7266 individuals from the Finnish GeneRISK cohort and sought for replication using independent data from 2045 participants. Significant sex differences in the levels of 141 lipid species were observed (P<7.0×10-4). Interestingly, 121 lipid species showed significant age-sex interactions, with opposite age-related changes in 39 lipid species. In general, most of the cholesteryl esters, ceramides, lysophospholipids, and glycerides were higher in 45- to 50-year-old men compared with women of same age, but the sex differences narrowed down or reversed with age. We did not observe any major differences in genetic effect in the sex-stratified genome-wide association analyses, which suggests that common genetic variants do not have a major role in sex differences in lipidome. Conclusions Our study provides a comprehensive view of sex differences in circulatory lipids pointing to potential sex differences in lipid metabolism and highlights the need for sex- and age-specific prevention strategies.

Sex Differences in Lipid Metabolism: Implications for Systemic Lupus Erythematosus and Cardiovascular Disease Risk.

It is known that healthy women during childbearing years have a lower risk of cardiovascular disease (CVD) and coronary heart disease compared to age matched men. Various traditional risk factors have been shown to confer differential CVD susceptibilities by sex. Atherosclerosis is a major cause of CVD and mortality and sex differences in CVD risk could be due to reduced atherogenic low and very low-density lipoproteins (LDL and VLDL) and increased atheroprotective high density lipoproteins (HDLs) in women. In contrast, patients with systemic lupus erythematosus (SLE), a chronic inflammatory disease that predominately affects women, have an increased atherosclerotic and CVD risk. This increased CVD risk is largely associated with dyslipidaemia, the imbalance of atherogenic and atheroprotective lipoproteins, a conventional CVD risk factor. In many women with SLE, dyslipidaemia is characterised by elevated LDL and reduced HDL, eradicating the sex-specific CVD protection observed in healthy women compared to men. This review will explore this paradox, reporting what is known regarding sex differences in lipid metabolism and CVD risk in the healthy population and transgender individuals undergoing cross-sex hormone therapy, and provide evidence for how these differences may be compromised in an autoimmune inflammatory disease setting. This could lead to better understanding of mechanistic changes in lipid metabolism driving the increased CVD risk by sex and in autoimmunity and highlight potential therapeutic targets to help reduce this risk.

Sex differences in endurance exercise capacity and skeletal muscle lipid metabolism in mice.

Previous studies suggest that sex differences in lipid metabolism exist with females demonstrating a higher utilization of lipids during exercise, which is mediated partly by increased utilization of muscle triglycerides. However, whether these changes in lipid metabolism contribute directly to endurance exercise performance is unclear. Therefore, the objective of this study was to investigate the contribution of exercise substrate metabolism to sex differences in endurance exercise capacity (EEC) in mice. Male and female C57BL/6‐NCrl mice were subjected to an EEC test until exhaustion on a motorized treadmill. The treadmill was set at a 10% incline, and the speed gradually increased from 10.2 m/min to 22.2 m/min at fixed intervals for up to 2.5 h. Tissues and blood were harvested in mice immediately following the EEC. A cohort of sedentary, non‐exercised male and female mice were used as controls. Females outperformed males by ~25% on the EEC. Serum levels of both fatty acids and ketone bodies were ~50% higher in females at the end of the EEC. In sedentary female mice, skeletal muscle triglyceride content was significantly greater compared to sedentary males. Gene expression analysis demonstrated that genes involved in skeletal muscle fatty acid oxidation were significantly higher in females with no changes in genes associated with glucose uptake or ketone body oxidation. The findings suggest that female mice have a higher endurance exercise capacity and a greater ability to mobilize and utilize fatty acids for energy.

Correlation of Lipid Profile with Inflammatory Markers among COVID-19 Positive Patients: A Retrospective Study

Introduction: Lipids are fundamental biomolecules of the body. Infections like COVID-19 with intricate immune response in some patient’s leads to acute complications by affecting metabolic pathways at multiple levels. Metabolism of cholesterol, triglyceride and High Density Lipoprotein (HDL)-Cholesterol is deranged by cytokines and multiple inflammatory mediators. The sex differences in lipid metabolism may contribute in susceptibility, severity and outcome of Coronavirus Disease 2019 (COVID-19). Performing lipid profile in COVID-19 patient may help in assessing severity and prognosis of disease. Aim: To assess the relationship between lipid profile and inflammatory markers in COVID-19 patients and also to evaluate the gender wise differences in lipid parameters and their correlations with inflammatory markers. Materials and Methods: This retrospective study was conducted in Department of Biochemistry at SHKM, GMC, Mewat, Haryana, India (tertiary care health centre) on COVID-19 positive patients attending Outpatient Department (OPD) and Inpatient Department (IPD), from October 2020 to December 2020. The data of 85 patients with COVID-19 positive, confirmed by Reverse Transcription-Polymerase Chain Reaction (RT-PCR) and who were prescribed for lipid profile along with C-Reactive Protein (CRP) and serum ferritin were included in the study. Serum total cholesterol, triglyceride, HDL-Cholesterol, CRP and ferritin were measured in the subjects. Data was statistically analysed using Student’s t test and Pearson correlation coefficient. Results: Total 85 (46 males and 39 females) COVID-19 patients were included in the study. Mean age in male and female patients were 43.02±15.52 years and 42.02±15.25 years, respectively with a range of 5-82 years. Mean value of Serum triglycerides, HDL-C and total cholesterol was 204.94±141.27 mg/dL, 42.97±13.38 mg/ dL and 187.058±45.75 mg/dL, respectively. Serum triglycerides were statistically significantly higher in males than females (pvalue=0.0413). The HDL-C however was significantly higher in females than males (p-value=0.0006). In male patients, r-value between cholesterol and CRP was -0.3538, and p-value was 0.016. Ferritin had a significant negative correlation with HDL-C (r-value=-0.3578, p-value=0.00079). Weak Positive correlation was noted between triglyceride and ferritin (r-value= 0.2285, p-value=0.035). Conclusion: High levels of serum triglycerides, low total cholesterol, and low HDL-cholesterol correlates with inflammatory markers like CRP and ferritin in COVID-19 patients. Lipid profile may be used as a potential marker in all COVID-19 patients in assessing prognosis of disease.

Sex difference in lipid levels in first-diagnosed drug-naïve depression patients: A case-control and 12-weeks follow-up study

Aim Patients with depression have a high prevalence of developing dyslipidemia. In this study, we aim to investigate the difference of serum lipids, including total cholesterol (TCH), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglycerides (TG), between the depressed patients and healthy controls. Sex differences in lipids and their psychological correlations were also included. Methods The study included 56 healthy controls (males/females = 26/30) and 110 first-diagnosed drug-naïve outpatients (males/females = 35/75). A total of 42 patients (males/females = 14/28) were followed for 3 months. Results A significant difference was found in TCH and LDL-C among healthy control and patients. Interestingly, female patients with first-diagnosed, drug-naïve depression had lower atherogenic indices than male patients. After 3 months of antidepressants therapy, female patients exhibited detrimental changes in serum lipids, namely increased TG and atherogenic index. Moreover, correlation analysis showed significant correlations between changes of depression inventory (HAMD and BDI) score and serum lipids (TCH, HDL-C) in depressed patients. Conclusion We found that dyslipidemia was more common in female patients with depression during therapy with antidepressants. Moreover, the altered serum lipids and atherogenic index might be a hallmark of female patients. Further investigation of sex differences in lipid metabolism of depression is warranted.

517-P: Cardiometabolic Benefits in Older Adults with Metabolic Syndrome after Diabetes Prevention Program (DPP)-Based Lifestyle Intervention

Nearly 50% of US adults >60 years have metabolic syndrome (MetS), which is linked to heart disease and diabetes. We evaluated if changes in cardiometabolic measures during a behavioral weight loss intervention for older adults differed by baseline MetS status (+ vs. -). The Pitt Retiree Study (PRS) was a 1-year lifestyle intervention trial adapted from DPP for adults 65+ years at high cardiometabolic risk. Participants attended 12 in-person group sessions, then were randomized to a monthly follow-up mode (phone or newsletter). Goals included 7% weight loss by 4 months via reduced calorie/fat intake, increased lean protein, and aerobic/strength training. Analyses include women only as 77% of PRS was female and sex differences in lipid metabolism exist. Participants (n=238) were mean (SD) age 71.1 (4.2), BMI 33.8 (5.4), and 67% had MetS at baseline. Regression models were used to compare change in cardiometabolic measures at 12 months in -MetS vs. +MetS (Table). Mean triglycerides (TG) decreased more in +MetS than -MetS while changes in other cardiometabolic measures did not differ between groups. -MetS had normal mean TG at baseline with little scope to improve, while +MetS had controlled blood pressure (BP) and LDL due to greater use of BP and lipid-lowering drugs. Nevertheless, both groups showed favorable cardiometabolic changes following lifestyle intervention. Disclosure H. J. Stern: None. R. G. Miller: None. T. J. Orchard: None. T. Costacou: None. E. M. Venditti: None. Funding National Institute of Diabetes and Digestive and Kidney Diseases (R18DK096405)

Sex differences in lipid metabolism are affected by presence of the gut microbiota

Physiological processes are differentially regulated between men and women. Sex and gut microbiota have each been demonstrated to regulate host metabolism, but it is unclear whether both factors are interdependent. Here, we determined to what extent sex-specific differences in lipid metabolism are modulated via the gut microbiota. While male and female Conv mice showed predominantly differential expression in gene sets related to lipid metabolism, GF mice showed differences in gene sets linked to gut health and inflammatory responses. This suggests that presence of the gut microbiota is important in sex-specific regulation of lipid metabolism. Further, we explored the role of bile acids as mediators in the cross-talk between the microbiome and host lipid metabolism. Females showed higher total and primary serum bile acids levels, independent of presence of microbiota. However, in presence of microbiota we observed higher secondary serum bile acid levels in females compared to males. Analysis of microbiota composition displayed sex-specific differences in Conv mice. Therefore, our data suggests that bile acids possibly play a role in the crosstalk between the microbiome and sex-specific regulation of lipid metabolism. In conclusion, our data shows that presence of the gut microbiota contributes to sex differences in lipid metabolism.

Sleep and metabolism: you sleep what you eat?

Sleep is generated by the brain, but sleep certainly does not only impact brain function. Several epidemiological studies and interventional studies have provided evidence for an association between sleep parameters and sleep duration, and outcomes such as body mass index and cardiovascular risk factors. However, how strong and clinically significant are these associations, and what happens to sleep if we change energy balance? Are there associations between what we eat and how we sleep? These questions are addressed in several papers concerning the interactions of sleep and metabolism in the first issue of the Journal of Sleep Research in 2014. In a prospective population-based cohort study in 1481 children, Berentzen and colleagues analysed the association between school-week sleep measures such as sleep duration and sleep timing, sleep quality as derived from indicators of nocturnal awakenings and daytime functioning, and cardiometabolic markers (Berentzen et al., 2014). The latter included anthropometry measurements (height, weight, etc.) as well as total cholesterol, high-density lipoprotein cholesterol and glycated haemoglobin (HbA1c), which is an indicator of the average blood glucose levels in the preceding months. The main findings of the study are that there are associations between sleep measures and some metabolic measures, and primarily so in girls, and not in boys. The associations observed in the girls were in the expected direction. Thus, longer sleep was associated with lower body mass index and smaller waist circumference and going to sleep late and rising early was associated with higher cholesterol. Importantly, and as pointed out by the authors, the effect sizes were relatively small, and the clinical significance of the associations is questioned by the authors. Profound sex differences are also reported in a study of anthropometric and metabolic markers as predictors of severity of obstructive sleep apnea (Mazzuca et al., 2014). These two studies, together with the well-documented sex differences in lipid metabolism (Sugiyama and Agellon, 2012) and sleep and circadian rhythms (Mong et al., 2011), highlight the importance of considering sex differences in studies in which the associations between sleep and metabolic markers are considered. If there are important interactions between sleep and metabolism it may be expected that not only how much we eat but also what we eat influences our sleep. Gradner and colleagues address this question in an analysis of the intake of specific dietary nutrients and aspects of sleep in a representative sample of adults (n = 4548) in the United States (Grandner et al., 2014). The aspects of sleep assessed included difficulties initiating and maintaining sleep as well as non-restorative sleep and daytime sleepiness. Diet and nutrient data were based on a 24-h recall procedure. A number of dietary components/nutrients were identified as contributing to the variance explained for the various sleep variables, i.e. difficulty falling asleep, difficulty maintaining sleep, etc. These include well-known contributors to a healthy diet, such as selenium, alpha carotene, calcium and vitamin D. How these associations will hold up in subsequent studies and whether associations will also be observed for objectively assessed sleep remains to be investigated. Nevertheless, the study provides a starting-point for other studies in this important area, for which there is also a substantial interest in the general population. We are often asked: ‘is it true that what you eat in the evening affects your sleep?’. The closely related question, ‘does it matter when we eat?’, is addressed in a study on the effects of intermittent fasting, such as occurs during Ramadan. In this study, food and water intake was restricted to the hours of darkness, while the sleep schedule and caloric intake were controlled (Bahammam et al., 2014). It is reported that whereas total sleep time and non-rapid eye movement (NREM) sleep were not significantly affected, a reduction in REM% was observed. The authors offer several explanations for this effect of a change in the ‘circadian’ pattern of food and water intake on sleep, and this study provides initial evidence that the timing of food and water intake also affects sleep in humans. Overall, these studies highlight the interactions between sleep, metabolism and circadian rhythmicity, an area of research in which, at a basic level, considerable progress has been made in the identification of the molecular elements contributing to these interactions (Bass, 2012).

Sex differences in lipid metabolism and metabolic disease risk

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.

Estrogen Deficiency after Menopause Does Not Result in Male Very-Low-Density Lipoprotein Metabolism Phenotype

Sex differences in lipid metabolism result in a less proatherogenic plasma lipid profile in premenopausal women than men. The mechanisms responsible for this are unclear but are thought to be related to differences in the sex hormone milieu in men and women. Our objective was to evaluate the effect of endogenous sex hormones on very-low-density lipoprotein (VLDL) triglyceride (TG) and apolipoprotein B-100 (apoB-100) metabolism. EXPERIMENTAL DESIGN AND MAIN OUTCOME MEASURES: We measured basal VLDL-TG and VLDL-apoB-100 concentrations and kinetics by using stable isotope-labeled tracers. Eight premenopausal women [age, 43 + or - 8 yr; body mass index (BMI), 35 + or - 4 kg/m(2); mean + or - sd], eight postmenopausal women (age, 55 + or - 4 yr; BMI, 34 + or - 4 kg/m(2)), and eight men (age, 41 + or - 13 yr; BMI, 34 + or - 4 kg/m(2)) were studied at Washington University School of Medicine, St. Louis, MO. VLDL-TG secretion rate was approximately double (P < 0.05) in postmenopausal women and men compared with premenopausal women but not different in postmenopausal women and men. The secretion rate of VLDL-apoB-100 was not different in pre- and postmenopausal women but was greater (P < 0.05) in men than in women. Endogenous ovarian sex steroids are responsible for sexual dimorphism in VLDL-TG secretion, whereas VLDL-apoB-100 secretion is not regulated by female reproductive hormones.

Sex differences in lipid metabolism during reproduction in free-living tree lizards ( Urosaurus ornatus)

Understanding the relationship between energy metabolism and signals that regulate reproduction may provide insight into the coordination of the energetically costly behavioral and physiological events that occur during reproduction. Significant changes in the utilization of stored lipids may occur during reproduction and the patterns of utilization observed often differ between females and males. Changes in levels of stored lipid reserves have been described extensively in animals from many taxa, but detailed biochemical analyses of alterations in the enzymes and substrates regulating lipid metabolism during periods of active reproductive effort rarely have been performed. In addition, few studies have compared males and females from the same population during the same reproductive season. In this study we examined lipid metabolism in free-living female and male tree lizards across a single reproductive season. We measured lipid stores, circulating lipid substrates, and the activities of enzymes regulating lipid storage and release in both liver and adipose tissue. Overall, females and males showed significant variation in abdominal fat body mass, liver total lipid, the activity of an enzyme regulating fat storage (DGAT) in both of these tissues, and circulating free fatty acids across the reproductive season. In females, total fat body mass, adipose DGAT, liver lipid, and liver DGAT significantly varied across reproductive stage, with vitellogenic and Gravid females often at opposite extremes. In males, fat body mass and liver fat varied across reproductive stage (without significant variation in DGAT in either tissue), as did circulating glycerol and free fatty acids. Correlations among sex steroid hormone levels and lipid metabolism variables suggested a role for these hormones in producing the patterns observed in each sex and in the observed sex differences lipid metabolism.

Alterations in plasma lipids in the presence of mild glucose intolerance in the offspring of two type II diabetic parents.

Plasma lipids and oral glucose tolerance were determined in 67 normal control subjects (age range 19-67 yr) and 150 individuals (17-69 yr) who were offspring of two type II diabetic parents. Age- and weight-adjusted analyses of covariance were performed for lipids and for glucose and insulin responses. For both men and women, the mean concentrations of total, low-density-, and high-density-lipoprotein-cholesterol and of triglycerides in the offspring with normal glucose tolerance (N = 109) were similar to respective controls. For offspring with abnormal glucose tolerance (N = 41), the mean levels of total cholesterol, LDL-cholesterol, and triglycerides were significantly elevated (P = 0.02 or less) in women but not in men. The mean HDL-cholesterol levels were 20% lower and LDL/HDL-cholesterol ratios 60% greater in women with abnormal glucose tolerance, whereas no significant differences existed for any of the lipid fractions in men, compared with respective controls. Both men and women with abnormal glucose tolerance had a comparable magnitude of hyperglycemia as well as hyperinsulinemia. These observations indicate that significant alterations in plasma lipids exist in individuals with mild, asymptomatic glucose intolerance and there are important sex differences in lipid metabolism in the early stage of diabetes, despite comparable degrees of glucose intolerance and insulin responses.

Studies on the role of phospholipids in the triglyceride cycle. II. Turnover of plasma phospholipids in ethionine-treated dogs.

AbstractThe disappearance of native labeled plasma phospholipids (nPLP32) was abruptly halted in the plasma of normal mongrel dogs shortly after givingdl‐ethionine by intraperitoneal injection. In other dogs, chronic feeding of ethionine over a period of three days prior to these measurements prolonged the turnover time of plasma phospholipids. This impairment in the turnover of plasma PL brought about by ethionine administration occurs regardless of sex differences in lipid metabolism or other physiological differences relating to the nutritional status of the animal. The amount of nPLP32 found in the liver at the end of the turnover experiments was also measured. These data suggest that phospholipid transport from plasma to liver is not impaired by ethionine. The possible significance of an ethionine‐induced choline deficiency which impairs transport of triglycerides and phospholipids from the liver to plasma is considered in regard to the role of phospholipids in the triglyceride cycle.