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Metabolites
Special Issues
Adipose Tissue, Reproduction and Metabolic Health in Women
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Adipose Tissue, Reproduction and Metabolic Health in Women

A special issue of Metabolites (ISSN 2218-1989). This special issue belongs to the section "Endocrinology and Clinical Metabolic Research".

Deadline for manuscript submissions: closed (5 March 2025) | Viewed by 8057

Special Issue Editors

Dr. Aldo Ferreira-Hermosillo

E-Mail Website
Guest Editor
Unidad de Investigación Médica en Enfermedades Endocrinas, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Mexico City, Mexico
Interests: obesity; metabolic syndrome; diabetes; adiposity
Dr. Renata Saucedo

E-Mail Website
Guest Editor
Unidad de Investigación Médica en Enfermedades Endocrinas, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Mexico City, Mexico
Interests: gestational diabetes; type 2 diabetes; hormone replacement therapy; obesity

Special Issue Information

Dear Colleagues,

The prevalence of obesity has increased worldwide, particularly in the female population, affecting up to 30% of women of reproductive age. Besides its association with diabetes, hypertension, dyslipidemia, obstructive sleep apnea, metabolic-dysfunction-associated fatty liver disease (previously known as non-alcoholic fatty liver disease), and cardiovascular comorbidities, obesity also has multiple consequences in the reproductive axis, increasing the risk of infertility, miscarriage, and polycystic ovarian syndrome; during the pregnancy due its association with gestational diabetes and preeclampsia; and in offspring, being a risk factor for congenital anomalies, macrosomia, preterm birth, and the development of obesity and metabolic syndrome. It has been reported that these reproductive diseases are correlated with obesity due to an increased amount of adipose tissue and a higher number of infiltrating immune cells that produce adipokines, cytokines, and oxidative stress products.

This Special Issue, “Adipose Tissue, Reproduction and Metabolic Health in Women”, focuses on the reproductive consequences of increased adiposity for women from a molecular and translational approach. We are interested in original research, review articles, and meta-analyses describing metabolites and metabolic pathways, metabolic perturbations induced by drugs, the impact of nutrients and environment on metabolic pathways, and the development of a methodology for detecting metabolites or changes in metabolic pathways. Contributions addressing topics such as infertility, gestational diabetes, obesity during pregnancy and its consequences, preeclampsia, and polycystic ovarian syndrome are also welcome. Finally, other topics related to adiposity and reproductive challenges that are within the scope of the journal will be considered.

Dr. Aldo Ferreira-Hermosillo
Dr. Renata Saucedo
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Metabolites is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • adiposity
  • gestational diabetes
  • preeclampsia
  • pregnancy
  • obesity
  • polycystic ovarian syndrome
  • infertility
  • reproductive health

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Published Papers (5 papers)

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Research

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12 pages, 636 KiB  
Article
Longitudinal Trajectory of Free Fatty Acids in Pregnancy According to First-Trimester Maternal Metabolic Status and the Presence of Gestational Diabetes
by Otilia Perichart-Perera, Isabel González-Ludlow, Omar Piña-Ramírez, Maricruz Tolentino-Dolores, Guadalupe Estrada-Gutierrez, Sandra B. Parra-Hernández, Maribel Sánchez-Martínez, Omar Granados-Portillo and Ameyalli M. Rodríguez-Cano
Metabolites 2025, 15(5), 320; https://doi.org/10.3390/metabo15050320 - 11 May 2025
Viewed by 638
Abstract
Background/Objectives: Maternal free fatty acids (FFAs) play a critical role in maternal metabolism, fetal growth, and pregnancy outcomes. However, their relationship with maternal metabolic status in early pregnancy and the subsequent development of gestational diabetes mellitus (GDM) remains unclear. Aim: Assess the trajectory [...] Read more.
Background/Objectives: Maternal free fatty acids (FFAs) play a critical role in maternal metabolism, fetal growth, and pregnancy outcomes. However, their relationship with maternal metabolic status in early pregnancy and the subsequent development of gestational diabetes mellitus (GDM) remains unclear. Aim: Assess the trajectory of FFA concentrations during pregnancy, considering first-trimester metabolic status (obesity, insulin resistance—IR) and the development of GDM, and evaluate whether first-trimester FFA is a relevant risk factor for GDM. Methods: A case–control study nested within the OBESO cohort (Mexico City, pregnant women and their children), classified women according to first-trimester metabolic status (pregestational body mass index—pBMI, insulin resistance homeostasis model assessment—HOMA-IR > 1.6), as well as the presence of GDM: Group 1 (normal weight without IR, n = 60), Group 2 (obesity without IR, no GDM, n = 20), Group 3 (obesity with IR, no GDM, n = 20), and Group 4 (obesity with IR, with GDM, n = 9). FFA concentrations were measured each trimester. Statistical analyses included repeated measures ANOVA and logistic regression models. Results: FFA concentrations were the highest in Group 4 across all trimesters (p < 0.05). FFAs decreased throughout pregnancy in all groups (p = 0.023), with the most significant decline from the first to the third trimester (p < 0.001). The greatest reduction occurred in Group 4 (p < 0.001), followed by Group 3. Multivariate logistic regression showed no association between first-trimester FFAs and the development of GDM. Higher gestational weight gain was associated with a higher GDM risk (OR: 1.22, 95%CI: 1.01–1.48), when the FFAs difference was accounted for. Conclusions: FFA levels are higher in women with GDM compared with women with obesity or a normal weight. However, FFAs progressively decline from the first to the third trimester, with the most pronounced decrease in women with obesity, IR, and GDM. Full article
(This article belongs to the Special Issue Adipose Tissue, Reproduction and Metabolic Health in Women)
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Review

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17 pages, 1059 KiB  
Review
Metabolic Changes in Patients with Premature Ovarian Insufficiency: Adipose Tissue Focus—A Narrative Review
by Miriam Sánchez-García, Kapy León-Wu, Regina de Miguel-Ibáñez, Nitzia López-Juárez, Claudia Ramírez-Rentería, Etual Espinosa-Cárdenas, Ernesto Sosa-Eroza and Manuel R. García-Sáenz
Metabolites 2025, 15(4), 242; https://doi.org/10.3390/metabo15040242 - 2 Apr 2025
Viewed by 1734
Abstract
Background: Estrogen plays a crucial role in adipose tissue homeostasis, influencing fat distribution, lipid metabolism, and insulin sensitivity. Through estrogen receptor (ER) activation, particularly ERα, estradiol (E2) regulates adipogenesis, inhibits adipocyte hypertrophy, and promotes insulin signaling. It enhances lipid oxidation, reduces lipogenesis, and [...] Read more.
Background: Estrogen plays a crucial role in adipose tissue homeostasis, influencing fat distribution, lipid metabolism, and insulin sensitivity. Through estrogen receptor (ER) activation, particularly ERα, estradiol (E2) regulates adipogenesis, inhibits adipocyte hypertrophy, and promotes insulin signaling. It enhances lipid oxidation, reduces lipogenesis, and suppresses pro-inflammatory cytokine production, thereby maintaining metabolic health. Primary ovarian insufficiency (POI), characterized by estrogen deficiency before the age of 40, disrupts this regulatory network, leading to adverse metabolic effects. Objetives: This review examines the effects of estrogen on adipose tissue, lipid metabolism, and carbohydrate metabolism, with a particular focus on clinical evidence in women with POI. Methods: A narrative review of the metabolic alterations associated with POI, emphasizing the molecular, biochemical, and metabolic mechanisms underlying estrogen deficiency, with a special focus on adipose tissue. Results: Women with POI exhibit increased visceral fat accumulation, reduced lean mass, and alterations in adipokine secretion, resembling the metabolic phenotype of postmenopausal women. The decline in estrogen levels contributes to central adiposity, impaired lipid metabolism, and insulin resistance, exacerbating the risk of type 2 diabetes (T2D) and cardiovascular disease (CVD). The loss of estrogenic regulation leads to enhanced lipolysis in visceral fat, raising free fatty acid flux to the liver, promoting hepatic steatosis, and worsening insulin resistance. Studies indicate that POI patients have significantly higher total cholesterol, low-density lipoprotein (LDL) cholesterol, and triglycerides compared to age-matched controls, reinforcing their heightened CVD risk. Reduced sex hormone-binding globulin (SHBG) levels increase free androgen availability, aggravating central fat deposition. These metabolic disturbances can potentially accelerate atherosclerosis and vascular aging, increasing morbidity and mortality in POI patients. Conclusions: Understanding the role of estrogen in adipose tissue and its disruption in POI highlights the importance of early intervention. Although the available evidence is limited and largely extrapolated from menopause studies, strategies such as hormone replacement therapy, lifestyle modifications, and lipid profile optimization are essential to mitigate metabolic consequences and improve long-term health outcomes in women with POI. Full article
(This article belongs to the Special Issue Adipose Tissue, Reproduction and Metabolic Health in Women)
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11 pages, 1254 KiB  
Review
Introduction to the Proteomic Analysis of Placentas with Fetal Growth Restriction and Impaired Lipid Metabolism
by Malwina Sypiańska and Aleksandra Stupak
Metabolites 2024, 14(11), 632; https://doi.org/10.3390/metabo14110632 - 16 Nov 2024
Viewed by 1424
Abstract
Fetal growth restriction (FGR) is a disorder defined as the failure of a fetus to achieve its full biological development potential due to decreased placental function, which can be attributed to a range of reasons. FGR is linked to negative health outcomes during [...] Read more.
Fetal growth restriction (FGR) is a disorder defined as the failure of a fetus to achieve its full biological development potential due to decreased placental function, which can be attributed to a range of reasons. FGR is linked to negative health outcomes during the perinatal period, including increased morbidity and mortality. Long-term health problems, such as impaired neurological and cognitive development, as well as cardiovascular and endocrine diseases, have also been found in adulthood. Aspirin administered prophylactically to high-risk women can effectively prevent FGR. FGR pregnancy care comprises several steps, including the weekly assessment of several blood vessels using Doppler measurements, amniotic fluid index (AFI), estimated fetal weight (EFW), cardiotocography (CTG), as well as delivery by 37 weeks. Pregnancy is a complex condition characterized by metabolic adjustments that guarantee a consistent provision of vital metabolites allowing the fetus to grow and develop. The lipoprotein lipid physiology during pregnancy has significant consequences for both the fetus and baby, and for the mother. In the course of a typical pregnancy, cholesterol levels increase by roughly 50%, LDL-C (low-density lipoprotein cholesterol) levels by 30–40%, HDL-C by 25% (high-density lipoprotein cholesterol). Typically, there is also a 2- to 3-fold increase in triglycerides. Low maternal blood cholesterol levels during pregnancy are linked to a decrease in birth weight and an increased occurrence of microcephaly. FGR impacts the placenta during pregnancy, resulting in alterations in lipid metabolism. Research has been undertaken to distinguish variations in protein expression between normal placentas and those impacted by FGR. This can aid in comprehending the fundamental pathogenic mechanisms of FGR and perhaps pave the way for the creation of novel diagnostic and treatment methods. Commonly employed approaches for detecting and analyzing variations in placental proteomes include mass spectrometry, bioinformatic analysis, and various proteomic techniques. Full article
(This article belongs to the Special Issue Adipose Tissue, Reproduction and Metabolic Health in Women)
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18 pages, 337 KiB  
Review
Association of DNA Methylation with Infant Birth Weight in Women with Gestational Diabetes
by Renata Saucedo, Aldo Ferreira-Hermosillo, Magalhi Robledo-Clemente, Mary Flor Díaz-Velázquez and Jorge Valencia-Ortega
Metabolites 2024, 14(7), 361; https://doi.org/10.3390/metabo14070361 - 27 Jun 2024
Cited by 1 | Viewed by 2057
Abstract
Offspring exposed to gestational diabetes mellitus (GDM) exhibit greater adiposity at birth. This early-life phenotype may increase offspring risk of developing obesity, metabolic syndrome, type 2 diabetes, and cardiovascular disease later in life. Infants born to women with GDM have a dysregulation of [...] Read more.
Offspring exposed to gestational diabetes mellitus (GDM) exhibit greater adiposity at birth. This early-life phenotype may increase offspring risk of developing obesity, metabolic syndrome, type 2 diabetes, and cardiovascular disease later in life. Infants born to women with GDM have a dysregulation of several hormones, cytokines, and growth factors related to fetal fat mass growth. One of the molecular mechanisms of GDM influencing these factors is epigenetic alterations, such as DNA methylation (DNAm). This review will examine the role of DNAm as a potential biomarker for monitoring fetal growth during pregnancy in women with GDM. This information is relevant since it may provide useful new biomarkers for the diagnosis, prognosis, and treatment of fetal growth and its later-life health consequences. Full article
(This article belongs to the Special Issue Adipose Tissue, Reproduction and Metabolic Health in Women)

Other

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19 pages, 1772 KiB  
Systematic Review
Circulating MicroRNAs Associated with Changes in the Placenta and Their Possible Role in the Fetus During Gestational Diabetes Mellitus: A Review
by Ninna Leslie Trejo-Gonzalez, Martin Palomar-Morales, Luis Arturo Baiza-Gutman, Guadalupe Diaz-Rosas, Clara Ortega-Camarillo and Alejandra Contreras-Ramos
Metabolites 2025, 15(6), 367; https://doi.org/10.3390/metabo15060367 - 3 Jun 2025
Viewed by 621
Abstract
MicroRNAs (miRs) are epigenetic regulators of several metabolic diseases, including gestational diabetes mellitus (GDM). Objectives: Following a systematic review, we propose a pattern of key circulating miRs associated with placental changes and their potential role in the fetus. Methods: A systematic investigation of [...] Read more.
MicroRNAs (miRs) are epigenetic regulators of several metabolic diseases, including gestational diabetes mellitus (GDM). Objectives: Following a systematic review, we propose a pattern of key circulating miRs associated with placental changes and their potential role in the fetus. Methods: A systematic investigation of studies published between January 2011 and July 2024 was conducted in the PubMed, ScienceDirect, Trip Database, and Wiley databases. A total of 90 articles were analyzed. Results: Two hundred twenty-six circulating microRNAs were identified in women with GDM, and fifty miRs were validated by PCR, with miRs-16-5p, -29a-5p, and -195-5p being the most frequently reported. Interestingly, miR-16-5p was also expressed in the placenta but not in umbilical cord blood or amniotic fluid. Conversely, miR-126-3p was expressed in circulation, the placenta, umbilical cord blood, and amniotic fluid. Several reports describe high expression levels of miR-518d in maternal circulation, umbilical cord blood, and placenta. Controversial results regarding the expression of miR-29a-3p, -137, and -148a-3p were identified when comparing umbilical cord blood and the placenta. Conclusions: In silico analyses suggest that the miR-29 family, as well as miRs-16-5p, -126-3p, -195-5p, and -518b, may be involved in alterations in the heart, brain, and kidneys in the embryo when exposed to a hyperglycemic environment. Full article
(This article belongs to the Special Issue Adipose Tissue, Reproduction and Metabolic Health in Women)
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