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Sex Differences in Obesity, Insulin Resistance, Metabolic Syndrome, and the Microbiome

About the series

New data show that there are sex differences in the mechanisms responsible for insulin resistance, metabolic syndrome and obesity.  Furthermore, sex differences are also present in the gut microbiome which is important in maintaining levels of estrogens and androgens. The cardiometabolic consequences of sex differences in these tissues impact the development and prognosis for cardiovascular disease in men and women.

For these reasons, the Editors of Biology of Sex Differences have commissioned this thematic series on Sex Differences in Obesity, Insulin Resistance, Metabolic Syndrome and the Microbiome. This collection of commissioned review articles and original research papers provides an overview of what is known about sex differences as they relate to cardiometabolic health and obesity.  

  1. Scientific evidence highlights the influence of biological sex on the relationship between stress and metabolic dysfunctions. However, there is limited understanding of how diet and stress concurrently contrib...

    Authors: Sanutha Shetty, Samuel J. Duesman, Sanil Patel, Pacific Huynh, Pamela Toh, Sanjana Shroff, Anika Das, Disha Chowhan, Benjamin Keller, Johana Alvarez, Rachel Fisher-Foye, Robert Sebra, Kristin Beaumont, Cameron S. McAlpine, Prashant Rajbhandari and Abha K. Rajbhandari
    Citation: Biology of Sex Differences 2024 15:55
    Content type: Research Published on:

  2. Differences in immune responses between women and men are leading to a strong sex bias in the incidence of autoimmune diseases that predominantly affect women, such as multiple sclerosis (MS). MS manifests in ...

    Authors: Ingo Winschel, Anne Willing, Jan Broder Engler, Mark Walkenhorst, Nina Meurs, Lars Binkle-Ladisch, Marcel S. Woo, Lena Kristina Pfeffer, Jana K. Sonner, Uwe Borgmeyer, Sven Hendrik Hagen, Benjamin Grünhagel, Janna M. Claussen, Marcus Altfeld and Manuel A. Friese
    Citation: Biology of Sex Differences 2024 15:41
    Content type: Research Published on:

  3. Patients with depression, especially women, are associated with low bone mineral density (BMD). Traditional antidepressants are associated with negative effects on BMD. Few studies have examined the effect of ...

    Authors: Xiaofeng Lan, Haiyan Liu, Chengyu Wang, Weicheng Li, Fan Zhang, Zhibo Hu, Xiaoyu Chen, Zerui You, Yuping Ning and Yanling Zhou
    Citation: Biology of Sex Differences 2024 15:12
    Content type: Research Published on:

  4. Cardiovascular diseases (CVD), including coronary heart disease (CHD), display a higher prevalence in men than women. This study aims to evaluate the variations in the intestinal microbiota between men and wom...

    Authors: Helena Garcia-Fernandez, Antonio P. Arenas-de Larriva, Javier Lopez-Moreno, Francisco M. Gutierrez-Mariscal, Juan L. Romero-Cabrera, Helena Molina-Abril, Jose D. Torres-Peña, Diego Rodriguez-Cano, Maria M. Malagon, Jose M. Ordovas, Javier Delgado-Lista, Pablo Perez-Martinez, Jose Lopez-Miranda and Antonio Camargo
    Citation: Biology of Sex Differences 2024 15:7
    Content type: Research Published on:

  5. Recent decades have seen an exponential rise in global obesity prevalence, with rates nearly doubling in a span of 40 years. A comprehensive knowledge base regarding the systemic effects of obesity is required...

    Authors: Saluda Stapleton, Grace Welch, Lindsay DiBerardo and Linnea R Freeman
    Citation: Biology of Sex Differences 2024 15:5
    Content type: Research Published on:

  6. Over the past several decades, substantial ground has been gained in understanding the biology of sex differences. With new mandates to include sex as a biological variable in NIH-funded research, greater know...

    Authors: Meredith L. Johnson, Joshua D. Preston, Cetewayo S. Rashid, Kevin J. Pearson and J. Nina Ham
    Citation: Biology of Sex Differences 2023 14:88
    Content type: Commentary Published on:

  7. Adipose insulin resistance (Adipo-IR) is associated with multiple metabolic diseases, including non-alcoholic fatty liver disease (NAFLD). The study aimed to evaluate sex differences in the association between...

    Authors: Ying Wei, Jia Liu, Guang Wang and Ying Wang
    Citation: Biology of Sex Differences 2023 14:69
    Content type: Research Published on:

  8. Human endosomal Toll-like receptors TLR7 and TLR8 recognize self and non-self RNA ligands, and are important mediators of innate immunity and autoimmune pathogenesis. TLR7 and TLR8 are, respectively, encoded b...

    Authors: Ali Youness, Claire Cenac, Berenice Faz-López, Solange Grunenwald, Franck J. Barrat, Julie Chaumeil, José Enrique Mejía and Jean-Charles Guéry
    Citation: Biology of Sex Differences 2023 14:60
    Content type: Research Published on:

  9. The development and persistence of addiction is mediated in part by drug-induced alterations in nucleus accumbens (NAc) function. AMPA-type glutamate receptors (AMPARs) provide the main source of excitatory dr...

    Authors: Amanda M. Catalfio, Tracy L. Fetterly, Allison M. Nieto, Terry E. Robinson and Carrie R. Ferrario
    Citation: Biology of Sex Differences 2023 14:41
    Content type: Research Published on:

  10. This study investigated the effect of sex and age at type 2 diabetes (T2D) diagnosis on the influence of T2D-related genes, parental history of T2D, and obesity on T2D development.

    Authors: Jaime Berumen, Lorena Orozco, Héctor Gallardo-Rincón, Fernando Rivas, Elizabeth Barrera, Rosa E. Benuto, Humberto García-Ortiz, Melissa Marin-Medina, Eligia Juárez-Torres, Anabel Alvarado-Silva, Espiridión Ramos-Martinez, Luis Alberto MartÍnez-Juárez, Julieta Lomelín-Gascón, Alejandra Montoya, Janinne Ortega-Montiel, Diego-Abelardo Alvarez-Hernández…
    Citation: Biology of Sex Differences 2023 14:39
    Content type: Research Published on:

  11. As the housekeeping genes (HKG) generally involved in maintaining essential cell functions are typically assumed to exhibit constant expression levels across cell types, they are commonly employed as internal ...

    Authors: Maria Guaita-Cespedes, Rubén Grillo-Risco, Marta R. Hidalgo, Sonia Fernández-Veledo, Deborah Jane Burks, María de la Iglesia-Vayá, Amparo Galán and Francisco Garcia-Garcia
    Citation: Biology of Sex Differences 2023 14:20
    Content type: Research Published on:

  12. Obesity is accompanied by low-grade inflammation and leucocytosis and increases the risk of venous thromboembolism. Associations with platelet count, however, are unclear, because several studies have reported...

    Authors: Sofia Christakoudi, Konstantinos K. Tsilidis, Evangelos Evangelou and Elio Riboli
    Citation: Biology of Sex Differences 2023 14:12
    Content type: Research Published on:

  13. Whether the association of type 2 diabetes (T2DM) with dementia was differed by sex remains unclear, and the roles of age at onset of disease, insulin use and diabetes’ complications in their association are u...

    Authors: Chunmiao Zhou, Caiyun Dong, Ziwei Xie, Wenting Hao, Chunying Fu, Huizi Sun and Dongshan Zhu
    Citation: Biology of Sex Differences 2023 14:9
    Content type: Research Published on:

  14. Metabolic diseases, such as obesity, metabolic syndrome (MetS) and type 2 diabetes (T2D), are now a widespread pandemic in the developed world. These pathologies show sex differences in their development and p...

    Authors: Jose Antonio Santos-Marcos, Marina Mora-Ortiz, Manuel Tena-Sempere, Jose Lopez-Miranda and Antonio Camargo
    Citation: Biology of Sex Differences 2023 14:4
    Content type: Review Published on:

  15. Biological sex impacts susceptibility and presentation of cardiovascular disease, which remains the leading cause of death for both sexes. To reduce cardiovascular disease risk, statin drugs are commonly presc...

    Authors: Carrie B. Wiese, Zoey W. Agle, Peixiang Zhang and Karen Reue
    Citation: Biology of Sex Differences 2022 13:63
    Content type: Research Published on:

  16. Bile acids are known to be genotoxic and contribute to colorectal cancer (CRC). However, the link between CRC tumor bile acids to tumor location, patient sex, microbiome, immune-regulatory cells, and prognosis...

    Authors: Yuping Cai, Xinyi Shen, Lingeng Lu, Hong Yan, Huang Huang, Patricia Gaule, Engjel Muca, Casey M. Theriot, Zahra Rattray, Nicholas J. W. Rattray, Jun Lu, Nita Ahuja, Yawei Zhang, Philip B. Paty, Sajid A. Khan and Caroline H. Johnson
    Citation: Biology of Sex Differences 2022 13:61
    Content type: Research Published on:

  17. Studies on the association between urinary albumin-to-creatinine ratio (uACR) and diabetes are limited. We aimed to examine the association between uACR and diabetes among adults in the United States, with par...

    Authors: Yumeng Shi, Huan Hu, Zuxiang Wu, Ji Wu, Zhiqiang Chen and Ping Li
    Citation: Biology of Sex Differences 2022 13:53
    Content type: Research Published on:

  18. Adverse childhood experiences (ACEs) are an independent risk factor for chronic diseases, including type 2 diabetes, stroke and ischemic heart disease. However, the effect of ACEs considering sex and race are ...

    Authors: Jacqueline R. Leachman, Kory Heier, Feitong Lei, Nermin Ahmed, Carolina Dalmasso, Meredith S. Duncan and Analia S. Loria
    Citation: Biology of Sex Differences 2022 13:29
    Content type: Research Published on:

  20. Women attempt to quit smoking less often than men and are less likely to maintain abstinence. Reproductive hormones have been postulated as a reason for this sex difference, though this remains to be clarified...

    Authors: Ashley R. Ethier, Ty L. McKinney, Laurie Sykes Tottenham and Jennifer L. Gordon
    Citation: Biology of Sex Differences 2021 12:41
    Content type: Research Published on:

  21. To date, there is no clearly defined association between plasma selenium levels and first stroke. We aimed to investigate the association between baseline plasma selenium and first stroke risk in a community-b...

    Authors: Huan Hu, Chonglei Bi, Tengfei Lin, Lishun Liu, Yun Song, Binyan Wang, Ping Wang, Ziyi Zhou, Chongqian Fang, Hai Ma, Xiao Huang, Lihua Hu, Xiping Xu, Hao Zhang, Yong Huo, Xiaobin Wang…
    Citation: Biology of Sex Differences 2021 12:39
    Content type: Research Published on:

  22. A significant positive association was found in previous studies among obesity, visceral fat accumulation, and hyperuricemia. The purpose of this study was to explore the association between the ratio of visce...

    Authors: Xiao-He Wang, Wei-Ran Jiang, Min-Ying Zhang, Ying-Xin Shi, Yun-Ping Ji, Chun-Jun Li and Jing-Na Lin
    Citation: Biology of Sex Differences 2021 12:17
    Content type: Research Published on:

    The Correction to this article has been published in Biology of Sex Differences 2023 14:42

  23. Inadequate copper intake and increased fructose consumption represent two important nutritional problems in the USA. Dietary copper-fructose interactions alter gut microbial activity and contribute to the deve...

    Authors: Ming Song, Fang Yuan, Xiaohong Li, Xipeng Ma, Xinmin Yin, Eric C. Rouchka, Xiang Zhang, Zhongbin Deng, Russell A. Prough and Craig J. McClain
    Citation: Biology of Sex Differences 2021 12:3
    Content type: Research Published on:

  24. Pioglitazone is a promising therapeutic method for nonalcoholic fatty liver disease (NAFLD) patients with or without type 2 diabetes. However, there is remarkable variability in treatment response. We analyzed...

    Authors: Hongmei Yan, Weiyun Wu, Xinxia Chang, Mingfeng Xia, Sicheng Ma, Liu Wang and Jian Gao
    Citation: Biology of Sex Differences 2021 12:1
    Content type: Research Published on:

  25. Asparagine and aspartate homeostasis are linked with type 2 diabetes (T2D). This study aimed to explore whether asparagine and aspartate metabolism interacted with sex and age to increase the risk of T2D.

    Authors: Hui-Huan Luo, Xiao-Fei Feng, Xi-Lin Yang, Rui-Qin Hou and Zhong-Ze Fang
    Citation: Biology of Sex Differences 2020 11:58
    Content type: Research Published on:

  26. There are inconsistent interpretations of the interrelationship of adiposity, anthropometric indices, and blood pressure (BP) in hypertensive patients. Additionally, whether these relationships differ between ...

    Authors: Youzhou Chen, Zhuoli Zhang, Jihong Wang, Huayi Sun, Xingshan Zhao, Xiaoguang Cheng and Qiong Zhao
    Citation: Biology of Sex Differences 2020 11:38
    Content type: Research Published on:

  28. Obesity increases sympathetic nerve activity (SNA) in men, but not women. Here, we review current evidence suggesting that sexually dimorphic sympathoexcitatory responses to leptin and insulin may contribute. ...

    Authors: Zhigang Shi, Jennifer Wong and Virginia L. Brooks
    Citation: Biology of Sex Differences 2020 11:10
    Content type: Review Published on:

  29. Fibroblast growth factors (FGFs) belong to a large family comprising 22 FGF polypeptides that are widely expressed in tissues. Most of the FGFs can be secreted and involved in the regulation of skeletal muscle...

    Authors: Wei-hua Jia, Nuo-qi Wang, Lin Yin, Xi Chen, Bi-yu Hou, Jin-hua Wang, Gui-fen Qiang, Chi Bun Chan, Xiu-ying Yang and Guan-hua Du
    Citation: Biology of Sex Differences 2020 11:9
    Content type: Research Published on:

  30. Accumulating evidence indicates that high-fat diet (HFD)-induced metabolic disorders are associated with dysbiosis of the gut microbiota. However, the sex-specific characteristics of the gut microbiota and its...

    Authors: Chao Peng, Xinbo Xu, Yanshu Li, Xueyang Li, Xiaoyu Yang, Hongyan Chen, Yin Zhu, Nonghua Lu and Cong He
    Citation: Biology of Sex Differences 2020 11:5
    Content type: Research Published on:

  31. Diabetes is a strong risk factor for vascular disease. There is compelling evidence that the relative risk of vascular disease associated with diabetes is substantially higher in women than men. The mechanisms...

    Authors: Rianneke de Ritter, Marit de Jong, Rimke C. Vos, Carla J. H. van der Kallen, Simone J. S. Sep, Mark Woodward, Coen D. A. Stehouwer, Michiel L. Bots and Sanne A. E. Peters
    Citation: Biology of Sex Differences 2020 11:1
    Content type: Review Published on:

  32. Placental ischemia and hypertension, characteristic features of preeclampsia, are associated with impaired cerebral blood flow (CBF) autoregulation and cerebral edema. However, the factors that contribute to t...

    Authors: Junie P. Warrington, Fan Fan, Jeremy Duncan, Mark W. Cunningham, Babette B. LaMarca, Ralf Dechend, Gerd Wallukat, Richard J. Roman, Heather A. Drummond, Joey P. Granger and Michael J. Ryan
    Citation: Biology of Sex Differences 2019 10:58
    Content type: Research Published on:

  33. Males and females exhibit significant differences in metabolism and in brain ischemic stroke and different features of brain ischemic lesions are related to different health outcomes. It is critical to underst...

    Authors: Hailuan Zeng, Weibin Shi, Wenhai Jiang, Shengxiang Rao, Beijian Huang, Hongmei Yan and Xin Gao
    Citation: Biology of Sex Differences 2019 10:40
    Content type: Research Published on:

  34. Angiotensin-(1-7) is a beneficial hormone of the renin-angiotensin system known to play a positive role in regulation of blood pressure and glucose homeostasis. Previous studies have shown that in high-fat die...

    Authors: Melissa C. White, Amanda J. Miller, Justin Loloi, Sarah S. Bingaman, Biyi Shen, Ming Wang, Yuval Silberman, Sarah H. Lindsey and Amy C. Arnold
    Citation: Biology of Sex Differences 2019 10:36
    Content type: Research Published on:

  35. Although some recent studies have indicated an association between metabolic syndrome (MetS) and musculoskeletal disease, little is known about the association of MetS with low back pain (LBP). The present stu...

    Authors: Takahiko Yoshimoto, Hirotaka Ochiai, Takako Shirasawa, Satsue Nagahama, Akihito Uehara, Shogo Sai and Akatsuki Kokaze
    Citation: Biology of Sex Differences 2019 10:33
    Content type: Research Published on:

  37. It is well documented that the metabolic syndrome predisposes patients to increased cardiovascular risk. Emerging data indicates that cardiovascular risk conferred by metabolic syndrome is highly dependent on ...

    Authors: Jessica L. Faulkner and Eric J. Belin de Chantemèle
    Citation: Biology of Sex Differences 2019 10:30
    Content type: Review Published on:

  38. Key differences exist between men and women in the determinants and manifestations of cardiovascular and cardiometabolic diseases. Recently, gut microbiome-host relations have been implicated in cardiovascular...

    Authors: Alexander C. Razavi, Kaitlin S. Potts, Tanika N. Kelly and Lydia A. Bazzano
    Citation: Biology of Sex Differences 2019 10:29
    Content type: Review Published on:

  39. Adipocytes and macrophages, the two major constituents of adipose tissue, exhibit sex differences and work in synergy in adipose tissue physiology and pathophysiology, including obesity-linked insulin resistan...

    Authors: Yang Xin Zi Xu, Geetika Bassi and Suresh Mishra
    Citation: Biology of Sex Differences 2019 10:25
    Content type: Review Published on:

  41. Weight loss by surgery or lifestyle changes is strongly recommended for obese individuals to improve metabolic health, but the underlying impairments that persist from a history of obesity remain unclear. Rece...

    Authors: Cameron Griffin, Chelsea R. Hutch, Simin Abrishami, Daria Stelmak, Leila Eter, Ziru Li, Eric Chang, Devyani Agarwal, Brian Zamarron, Mita Varghese, Perla Subbaiah, Ormond A. MacDougald, Darleen A. Sandoval and Kanakadurga Singer
    Citation: Biology of Sex Differences 2019 10:16
    Content type: Research Published on: