Causes Of Sex Differences Research Articles

The host sex contributes to the endophytic bacterial community in Sargassum thunbergii and their receptacles.

Endophytic bacteria have a complex coevolutionary relationship with their host macroalgae. Dioecious macroalgae are important producers in marine ecosystems, but there is still a lack of research on how sex influences their endophytic bacteria. In this study, the endophytic bacterial communities in male and female S. thunbergii and their reproductive tissues (receptacles) were compared using culture methods and high-throughput sequencing. The endophytic bacterial communities detected by the two methods were different. Among the 78 isolated strains, the dominant phylum, genus, and species were Bacillota, Alkalihalobacillus, and Alkalihalobacillus algicola, respectively, in the algal bodies, while in the receptacles, they were Bacillota, Vibrio, and Vibrio alginolyticus. However, 24 phyla and 349 genera of endophytic bacteria were identified by high-throughput sequencing, and the dominant phylum and genus were Pseudomonadota and Sva0996_ Marine_ Group, respectively, in both the algal body and the receptacles. The two methods showed similar compositions of endophytic bacterial communities between the samples of different sexes, but the relative abundances of dominant and specific taxa were different. The high-throughput sequencing results showed more clearly that the sex of the host alga had an effect on its endophyte community assembly and a greater effect on the endophytic bacterial community in the receptacles. Moreover, most specific bacteria and predicted functional genes that differed between the samples from the males and females were related to metabolism, suggesting that metabolic differences are the main causes of sex differences in the endophytic bacterial community. Our research is the first to show that host sex contributes to the composition of endophytic bacterial communities in dioecious marine macroalgae. The results enrich the database of endophytic bacteria of dioecious marine macroalgae and pave the way for better understanding the assembly mechanism of the endophytic bacterial community of algae.

Causes of Sex Differences in Serum Cholesterol and Triglyceride Levels in Meishan Pigs.

To clarify the causes of sex differences (male < female) in the serum total cholesterol (TCHO) and triglyceride (TG) levels in Meishan pigs, we examined the sex differences in mRNA levels of key hepatic enzymes involved in the biosynthesis/metabolism of cholesterol and TG using real-time RT-PCR. There were no sex differences in mRNA levels of 3-hydroxy-3-methylglutaryl-CoA reductase and CYP51A1 for cholesterol biosynthesis, or of the rate-limiting enzyme CYP7A1 for bile acid synthesis from cholesterol. By contrast, sex differences (male < female) were observed in mRNA levels of glycerol-3-phosphate acyltransferase 1 (GPAT1), a rate-limiting enzyme for TG biosynthesis. However, the sex differences in mRNA levels of carnitine palmitoyltransferase 1A (CPT1A) and acyl-CoA dehydrogenase long chain (ACADL), key enzymes for the oxidation of the fatty acids that are structural components of TG, were the opposite (male > female). Castration of male pigs led to an increase in the mRNA level of GPAT1 and decreases in those of CPT1A and ACADL. Furthermore, testosterone propionate (TP)-treatment of castrated males and intact females restored and changed, respectively, these mRNA levels to those of intact males. Notably, castration and TP-treatment increased and decreased, respectively, serum and hepatic TG levels. These findings suggest that sex differences in the serum and hepatic TG levels in Meishan pigs are closely correlated with differences in testosterone-associated mRNA expression levels of the key enzymes (GPAT1, CPT1A, and ACADL) involved in the TG biosynthesis process, although no causes of sex differences in serum and hepatic TCHO levels could be found.

Escape from X-chromosome inactivation and sex differences in Alzheimer's disease.

Sex differences exist in the onset and progression of Alzheimer's disease. Globally, women have a higher prevalence, while men with Alzheimer's disease experience earlier mortality and more pronounced cognitive decline than women. The cause of sex differences in Alzheimer's disease remains unclear. Accumulating evidence suggests the potential role of X-linked genetic factors in the sex difference of Alzheimer's disease (AD). During embryogenesis, a remarkable process known as X-chromosome inactivation (XCI) occurs in females, leading to one of the X chromosomes undergoing transcriptional inactivation, which balances the effects of two X chromosomes in females. Nevertheless, certain genes exceptionally escape from XCI, which provides a basis for dual expression dosage of specific genes in females. Based on recent research findings, we explore key escape genes and their potential therapeutic use associated with Alzheimer's disease. Also, we discuss their possible role in driving the sex differences in Alzheimer's disease. This will provide new perspectives for precision medicine and gender-specific treatment of AD.

Hepatocyte-specific HDAC3 ablation promotes hepatocellular carcinoma in females by suppressing Foxa1/2

BackgroundHepatocellular carcinoma (HCC), the most common primary liver cancer, prevails mainly in males and has long been attributed to androgens and higher circumstantial levels of interleukin-6 (IL-6) produced by resident hepatic macrophages.MethodsConstitutively hepatocyte-specific histone deacetylase 3 (HDAC3)-deficient (HDAC3LCKO) mice and constitutively hepatocyte-specific HDAC3 knockout and systemic IL-6 simultaneously ablated (HDAC3LCKO& IL-6−/−) mice were used in our study to explore the causes of sex differences in HCC. Additionally, we performed human HCC tissues with an IHC score. Correlation analysis and linear regression plots were constructed to reveal the association between HDAC3 and its candidate genes. To further elucidate that HDAC3 controls the expression of Foxa1/2, we knocked down HDAC3 in HUH7 liver cancer cells.ResultsWe observed a contrary sex disparity, with an earlier onset and higher incidence of HCC in female mice when HDAC3 was selectively ablated in the liver. Loss of HDAC3 led to constant liver injury and the spontaneous development of HCC. Unlike the significant elevation of IL-6 in male mice at a very early age, female mice exhibit stable IL-6 levels, and IL-6 ablation did not eliminate the sex disparity in hepatocarcinogenesis in HDAC3-deficient mice. Oestrogen often protects the liver when combined with oestrogen receptor alpha (ERα); however, ovariectomy in HDAC3-ablated female mice significantly delayed tumourigenesis. The oestrogen-ERα axis can also play a role in tumour promotion in the absence of Foxa1 and Foxa2 in the receptor complex. Loss of HDAC3 profoundly reduced the expression of both Foxa1 and Foxa2 and impaired the binding between Foxa1/2 and ERα. Furthermore, a more frequent HDAC3 decrease accompanied by the simultaneous Foxa1/2 decline was found in female HCC compared to that in male HCC.ConclusionIn summary, we reported that loss of HDAC3 reduces Foxa1/2 and thus promotes HCC development in females in an oestrogen-dependent manner.

Agent-based models of the cultural evolution of occupational gender roles.

The causes of sex differences in human behaviour are contested, with 'evolutionary' and 'social' explanations often being pitted against each other in the literature. Recent work showing positive correlations between indices of gender equality and the size of sex differences in behaviour has been argued to show support for 'evolutionary' over 'social' approaches. This argument, however, neglects the potential for social learning to generate arbitrary gender segregation. In the current paper we simulate, using agent-based models, a population where agents exist as one of two 'types' and can use social information about which types of agents are performing which 'roles' within their environment. We find that agents self-segregate into different roles even where real differences in performance do not exist, if there is a common belief (modelled as priors) that group differences may exist in 'innate' competence. Facilitating role changes such that agents should move without cost to the predicted highest-rewards for their skills (i.e. fluidity of the labour market) reduced segregation, while forcing extended exploration of different roles eradicated gender segregation. These models are interpreted in terms of bio-cultural evolution, and the impact of social learning on the expression of gender roles.

Sex Differences in Long-Term Functional Decline after Ischemic Stroke: A Longitudinal Observational Study from the Fukuoka Stroke Registry

Introduction: Data on sex differences in poststroke functional status for a period longer than 1 year based on large cohorts are sparse. This study aimed to determine whether there are sex differences in long-term functional decline after ischemic stroke. Methods: We tracked functional status for 5 years among 3-month survivors of acute ischemic stroke and compared outcomes between women and men using a large-scale hospital-based stroke registry in Fukuoka, Japan. Functional status was assessed using the modified Rankin Scale (mRS). Functional dependency was defined as an mRS score of 3, 4, or 5. Logistic regression analysis was used to estimate odds ratios (ORs) and 95% confidence intervals of outcomes after adjusting for possible confounders. Results: A total of 8,446 patients (71.9 ± 12.5 years, 3,377 (40.0%) female patients) were enrolled in this study. Female sex was associated with a higher risk of functional dependency at 5 years poststroke even when adjusting for age, 3-month mRS score, and other confounding factors (multivariable-adjusted OR vs. men, 1.56 [95% confidence interval, 1.26–1.93]). This significant association of female sex with higher dependency at 5 years was also found among patients who were independent at 3 months poststroke. Subgroup analysis showed that increased risk of functional dependency in female patients was more marked in patients aged ≥75 years than in those aged <75 years (p for heterogeneity = 0.02). Conversely, female sex was associated with a lower risk of death. No sex difference was observed in stroke recurrence during 5 years poststroke. Discussion/Conclusion: This longitudinal observational study suggests that female sex was independently associated with an increased risk of functional decline in the chronic phase of stroke, especially in older patients. There was no sex difference in 5-year stroke recurrence, and thus, other factors might be involved in more significant deterioration of functional status in female survivors of ischemic stroke. Further studies are needed to elucidate underlying causes of sex differences in long-term functional decline after stroke.

Deciphering genetic causes for sex differences in human health through drug metabolism and transporter genes

Sex differences have been widely observed in human health. However, little is known about the underlying mechanism behind these observed sex differences. We hypothesize that sex-differentiated genetic effects are contributors of these phenotypic differences. Focusing on a collection of drug metabolism enzymes and transporters (DMET) genes, we discover sex-differentiated genetic regulatory mechanisms between these genes and human complex traits. Here, we show that sex-differentiated genetic effects were present at genome-level and at DMET gene regions for many human complex traits. These sex-differentiated regulatory mechanisms are reflected in the levels of gene expression and endogenous serum biomarkers. Through Mendelian Randomization analysis, we identify putative sex-differentiated causal effects in each sex separately. Furthermore, we identify and validate sex differential gene expression of a subset of DMET genes in human liver samples. We observe higher protein abundance and enzyme activity of CYP1A2 in male-derived liver microsomes, which leads to higher level of an active metabolite formation of clozapine, a commonly prescribed antipsychotic drug. Taken together, our results demonstrate the presence of sex-differentiated genetic effects on DMET gene regulation, which manifest in various phenotypic traits including disease risks and drug responses.

Verbal Abilities: Sex Differences in Children at Different Ages.

The assertion of sex differences in verbal abilities is a highly controversial subject. Some studies have demonstrated a female advantage; other studies have found higher rates in males. The results depended on the type of verbal ability that was studied, the cultural context, and the ages of the subjects. There are two types of theories that have been developed to explain the existence of sex differences in cognitive abilities. Social theories explain the differences as caused by social determinants. Biological theories consider biological factors such as prenatal development conditions and hormone levels, among others, as the cause of sex differences. To investigate sex differences in verbal abilities in children of different ages. Two different editions of Wechsler tests were used. For children age 2.5 to 5 years, the Wechsler Preschool Primary Scale of Intelligence (WPPSI-IV) was used. For children age 6 and older, we administered the Wechsler Intelligence Scale for Children (WISC-V). The total sample included 313 children. The study found significant sex differences in performance on the Verbal Comprehension Scale in children of different ages. At the age of 2 to 4 years, the girls performed better than the boys. In the group of boys, there was a significant increase in verbal abilities at the age of 8-9 years. By the age of 10-11 years, boys began outperforming girls on the Verbal Comprehension Index. Scores on the Verbal Comprehension and Visual Spatial subtests for the boy sample showed stronger correlations than in the girl sample in all age groups. Sex differences in verbal abilities varied depending on the age of the children. The boys showed a stronger integration of their verbal abilities into the structure of their intelligence than the girls.

Bateman gradients from first principles

In 1948, Angus Bateman presented experiments and concepts that remain influential and debated in sexual selection. The Bateman gradient relates reproductive success to mate number, and Bateman presented this as the cause of intra-masculine selection. A deeper causal level was subsequently asserted: that the ultimate cause of sex differences in Bateman gradients is the sex difference in gamete numbers, an argument that remains controversial and without mathematical backup. Here I develop models showing how asymmetry in gamete numbers alone can generate steeper Bateman gradients in males. This conclusion remains when the further asymmetry of internal fertilisation is added to the model and fertilisation is efficient. Strong gamete limitation can push Bateman gradients towards equality under external fertilisation and reverse them under internal fertilisation. Thus, this study provides a mathematical formalisation of Bateman’s brief verbal claim, while demonstrating that the link between gamete number and Bateman gradients is not inevitable nor trivial.

Innate Immunity at the Core of Sex Differences in Osteoarthritic Pain?

Osteoarthritis (OA) is a progressive whole-joint disease; no disease-modifying drugs are currently available to stop or slow its process. Symptoms alleviation is the only treatment option. OA is the major cause of chronic pain in adults, with pain being the main symptom driving patients to seek medical help. OA pathophysiology is closely associated with the innate immune system, which is also closely linked to pain mediators leading to joint pain. Pain research has shown sex differences in the biology of pain, including sexually dimorphic responses from key cell types in the innate immune system. Not only is OA more prevalent in women than in men, but women patients also show worse OA outcomes, partially due to experiencing more pain symptoms despite having similar levels of structural damage. The cause of sex differences in OA and OA pain is poorly understood. This review provides an overview of the involvement of innate immunity in OA pain in joints and in the dorsal root ganglion. We summarize the emerging evidence of sex differences regarding innate immunity in OA pain. Our main goal with this review was to provide a scientific foundation for future research leading to alternative pain relief therapies targeting innate immunity that consider sex differences. This will ultimately lead to a more effective treatment of pain in both women and men.

Sex biases in infectious diseases research.

Reporting the distribution and inclusion of both males and females in immunology and infectious diseases research is improving, but rigorous analyses of differential outcomes between males and females, including mechanistic inquiries into the causes of sex differences, still lags behind.

Developmental sex differences in the peri-pubertal pattern of hypothalamic reproductive gene expression, including Kiss1 and Tac2, may contribute to sex differences in puberty onset

The mechanisms regulating puberty still remain elusive, as do the underlying causes for sex differences in puberty onset (girls before boys) and pubertal disorders. Neuroendocrine puberty onset is signified by increased pulsatile GnRH secretion, yet how and when various upstream reproductive neural circuits change developmentally to govern this process is poorly understood. We previously reported day-by-day peri-pubertal increases (Kiss1, Tac2) or decreases (Rfrp) in hypothalamic gene expression of female mice, with several brain mRNA changes preceding external pubertal markers. However, similar pubertal measures in males were not previously reported. Here, to identify possible neural sex differences underlying sex differences in puberty onset, we analyzed peri-pubertal males and directly compared them with female littermates. Kiss1 expression in male mice increased over the peri-pubertal period in both the AVPV and ARC nuclei but with lower levels than in females at several ages. Likewise, Tac2 expression in the male ARC increased between juvenile and older peri-pubertal stages but with levels lower than females at most ages. By contrast, both DMN Rfrp expressionand Rfrp neuronal activation strongly decreased in males between juvenile and peri-pubertal stages, but with similar levels as females. Neither ARC KNDy neuronal activation nor Kiss1r expression in GnRH neurons differed between males and females or changed with age. These findings delineate several peri-pubertal changes in neural populations in developing males, with notable sex differences in kisspeptin and NKB neuron developmental patterns. Whether these peri-pubertal hypothalamic sex differences underlie sex differences in puberty onset deserves future investigation.

Sex-specific aging in animals: Perspective and future directions.

Sex differences in aging occur in many animal species, and they include sex differences in lifespan, in the onset and progression of age‐associated decline, and in physiological and molecular markers of aging. Sex differences in aging vary greatly across the animal kingdom. For example, there are species with longer‐lived females, species where males live longer, and species lacking sex differences in lifespan. The underlying causes of sex differences in aging remain mostly unknown. Currently, we do not understand the molecular drivers of sex differences in aging, or whether they are related to the accepted hallmarks or pillars of aging or linked to other well‐characterized processes. In particular, understanding the role of sex‐determination mechanisms and sex differences in aging is relatively understudied. Here, we take a comparative, interdisciplinary approach to explore various hypotheses about how sex differences in aging arise. We discuss genomic, morphological, and environmental differences between the sexes and how these relate to sex differences in aging. Finally, we present some suggestions for future research in this area and provide recommendations for promising experimental designs.

Неонатальная воспалительная боль, когнитивная и стресс-реактивная функции у взрослых самцов и самок крыс

Repetitive neonatal pain may cause central nervous system disorders. Existing clinical data on the effect of neonatal pain on learning, memory and stress-reactivity of the hypothalamic-pituitary-adrenal axis (the HPA axis) are limited to adolescence and have mostly been obtained for male individuals. The mechanism of neonatal pain effect has not yet been researched. Ontogenetic studies carried out on different-sex specimen are crucial for prediction, prevention and treatment of adaptive behavioural disorders caused by neonatal pain stress. Lately, this has become even more relevant due to COVID-19 affecting new-borns in need of intensive therapy. In this study, the impact of neonatal inflammatory pain on adult cognition and hormonal stress response was investigated in male and female rats. Continuous neonatal pain was induced by hindpaw formalin injections on days one and two from birth. In adult rats, we assessed spatial learning and memory using the Morris water maze and evaluated HPA reactivity in response to the formalin test. No significant cognitive function differences were found between the experimental group of rats subjected to neonatal pain and the control group. Within the experimental group subjected to neonatal pain, males showed better long-term spatial memory than females. After testing the long-term memory, we evaluated HPA reactivity by corticosterone levels in response to a formalin test. This parameter was higher in males. Only females with neonatal pain showed differences between short-term and long-term memory, with poorer long-term memory. Possible causes of sex differences in the cognitive function and hormonal stress response in adult rats exposed to neonatal inflammatory pain are discussed.

Sex Differences in Respiratory Viral Pathogenesis and Treatments.

Biological sex affects the outcome of diverse respiratory viral infections. The pathogenesis of respiratory infections caused by viruses ranging from respiratory syncytial virus to influenza viruses and severe acute respiratory syndrome coronavirus 2 differs between the sexes across the life course. Generally, males are more susceptible to severe outcomes from respiratory viral infections at younger and older ages. During reproductive years (i.e., after puberty and prior to menopause), females are often at greater risk than males for severe outcomes. Pregnancy and biological sex affect the pathogenesis of respiratory viral infections. In addition to sex differences in the pathogenesis of disease, there are consistent sex differences in responses to treatments, with females often developing greater immune responses but experiencing more adverse reactions than males. Animal models provide mechanistic insights into the causes of sex differences in respiratory virus pathogenesis and treatment outcomes, where available.

An Insight into the Sex Differences in COVID-19 Patients: What are the Possible Causes?

Studies have reported a sex bias in case fatalities of COVID-19 patients. Moreover, it is observed that men have a higher risk of developing a severe form of the disease compared to women, highlighting the importance of disaggregated data of male and female COVID-19 patients. On the other hand, other factors (eg, hormonal levels and immune functions) also need to be addressed due to the effects of sex differences on the outcomes of COVID-19 patients. An insight into the underlying causes of sex differences in COVID-19 patients may provide an opportunity for better care of the patients or prevention of the disease. The current study reviews the reports concerning with the sex differences in COVID-19 patients. It is explained how sex can affect angiotensin converting enzyme-2 (ACE2), that is a key component for the pathogenesis of COVID-19, and summarized the gender differences in immune responses and how sex hormones are involved in immune processes. Furthermore, the available data about the impact of sex hormones on the immune functions of COVID-19 cases are looked into.

The age-dependent effect of pre-pubertal castration on anxiety-like behaviour in male rats.

Adolescence is considered to be a critical period of sex hormone action (re)organising the brain and determining the behavioural phenotype. Such organisational effects in the brain might be the cause of sex differences in some behavioural features. In this experiment, we aimed to examine the role of pubertal sex hormones in development of anxiety in male rats. Male rats underwent gonadectomy prior to puberty onset, and were tested for explorative and anxiety-like behaviour in adolescence as well as in young adulthood. In adolescence, but not in adulthood, gonadectomised rats spend by 50% more time (p<.05) in the centre zone of the open-field than sham-operated counterparts. Young adult gonadectomised rats showed approximately 1.5-fold greater exploratory activity, in both open field (p<.001) and elevated plus maze (p<.01), in comparison with young adult control rats. Our results indicate that pre-pubertal castration may have test-specific anxiolytic effect in adolescent male rats, and it may attenuate the decline in explorative behaviour in young adult males. These differences in short- and long-term effects of gonadectomy could explain some contradictory results of previous studies on the role of testosterone in anxiety-like behaviour of male rodents. Thus, the age-specific consequences of pre-pubertal hormone deprivation should be considered.

Sex-Associated Differences in Cardiac Reverse Remodeling in Patients Supported by Contemporary Left Ventricular Assist Devices

Women differ from men in their left ventricular (LV) structure, function and remodeling with age and diseases. The LV assist device (LVAD) unloads the LV and reversely remodels the heart. We sought to define the effects of sex on longitudinal reverse remodeling after LVAD implantation. Cardiac structure and function were assessed by serial echocardiograms. Mixed effect regression models were constructed to assess the independent contribution of sex to longitudinal changes in cardiac structure and function. A total of 355 consecutive patients with advanced heart failure received continuous flow LVADs between 2006 and 2016. The average age was 56 ± 13 years, 73% were men, and 67% were black. Early (within 3 months) after LVAD implantation, women had a greater reduction in LV dimensions and a greater increase in LV ejection fraction compared with men. These differences were independent of age, body surface area, device type, or ischemic etiology of heart failure. At long-term follow-up, LV dimensions increased slightly over time in women compared with men, but overall, earlier changes were maintained. Women had significantly more favorable longitudinal changes in cardiac structure and function in response to LV unloading compared with men. Understanding the cause of sex difference in reverse remodeling after LVAD may help to devise novel therapeutic strategies for women with advanced heart failure.

Sex Differences in Heart Failure—Female Representation in Heart Failure Studies

The prevalence of heart failure (HF) continues to grow in the USA, and approximately 50% of these patients are women. Despite this, there has been an underrepresentation of women in HF clinical trials, which has led to limitations in understanding of sex-related differences in HF pathophysiology, diagnosis, and treatment. The purpose of this review is to highlight the differences between men and women in various heart failure trials conducted in the last century and emphasize new findings from recent trials in the management of, and outcomes in, women with HF. HF trials have shown that women have improved survival with guideline-directed medical therapy, and the most recent analysis from PARADIGM-HF showed women had lower mortality and hospitalization rate compared with men. Furthermore, despite comprising only 20% of subjects in cardiac resynchronization therapy (CRT) trials, we now know that women are likely to benefit from a CRT device, in particular those with left bundle branch block. Advanced therapies for heart failure including durable mechanical circulatory support remain underused in women, and female patients are less likely to undergo heart transplantation when compared with men of similar risk profiles. The latest studies have shown women receiving continuous-flow left ventricular assist device support had lower chances of heart transplantation, increased risk of waitlist mortality, and higher rates of delisting for worsening clinical status. However, post transplantation, women have better survival when compared with men. Although several studies have shown that women with HF live longer than men, they experience greater self-reported psychological and physical disability and poorer overall quality of life. The cause of sex differences in morbidity and mortality remains unknown, but as the therapeutic options for HF expand, sex-based differences in treatment would need to be considered.

Sex Differences in Inflammatory Responses to Adipose Tissue Lipolysis in Diet-Induced Obesity.

Males are known to have profound adipose tissue macrophage (ATM) accumulation in gonadal white adipose tissue (GWAT) during obesity, whereas females are protected from such an inflammatory response even with increased adiposity. The inflammatory tone in males is linked to insulin resistance and might be the underlying cause for sex differences in metabolic disease. Factors regulating the meta-inflammatory response remain unclear but enhanced lipid storage in females may explain the reduced inflammatory response to high-fat diets. In this study, we evaluated lean and obese females with stimulated lipolysis to understand whether a stress release of free fatty acids (FFAs) could induce female ATMs. We demonstrate that in both lean and obese females, GWAT CD11c- resident ATMs accumulate with β-3 adrenergic receptor-stimulated lipolysis. Lipolysis elevated serum FFA, triglyceride, and IL-6 levels in females that corresponded to significant phosphorylated hormone-sensitive lipase and adipose triglyceride lipase protein expression in obese female GWAT compared with males. Increased lipolytic response in obese females was associated with crown-like structures and induced Il6, Mcp1, Arg1, and Mgl1 expression in obese female GWAT, suggesting an environment of lipid clearance and adipose remodeling. With this finding we next investigated whether lipid storage and lipolytic mediators differed by sex. Diacylglycerol, ceramides, phospholipids, and certain fatty acid species associated with inflammation were elevated in male GWAT compared with obese female GWAT. Overall, our data demonstrate a role for GWAT lipid storage and lipolytic metabolites to induce inflammation in males and induce remodeling in females that might explain sex differences in overall metabolic health.