Worldwide obesity is increasing at an alarming rate in children and adolescents, with the consequent emergence of co-morbidities. Moreover, the maternal environment during pregnancy plays an important role in obesity, contributing to transgenerational transmission of the same and metabolic dysfunction. White adipose tissue represents a prime target of metabolic programming induced by maternal milieu. In this article, we review adipose tissue physiology and development, as well as maternal influences during the perinatal period that may lead to obesity in early postnatal life and adulthood. First, we describe the adipose tissue cell composition, distribution and hormonal action, together with the evidence of hormonal factors participating in fetal/postnatal programming. Subsequently, we describe the critical periods of adipose tissue development and the relationship of gestational and early postnatal life with healthy fetal adipose tissue expansion. Furthermore, we discuss the evidence showing that adipose tissue is an important target for nutritional, hormonal and epigenetic signals to modulate fetal growth. Finally, we describe nutritional, hormonal, epigenetic and microbiome changes observed in maternal obesity, and whether their disruption alters fetal growth and adiposity. The presented evidence supports the developmental origins of health and disease concept, which proposes that the homeostatic system is affected during gestational and postnatal development, impeding the ability to regulate body weight after birth, thereby resulting in adult obesity. Consequently, we anticipate that promoting a healthy early-life programming of adipose tissue and increasing the knowledge of the mechanisms by which maternal factors affect the health of future generations may offer novel strategies for explaining and addressing worldwide health problems such as obesity.

Nonalcoholic fatty liver disease (NAFLD) is the main liver disease worldwide, and its prevalence in children and adolescents has been increasing in the past years. It has been demonstrated that parental exposure to different conditions, both preconceptionally and during pregnancy, can lead to fetal programming of several metabolic diseases, including NAFLD. In this article, we review some of the maternal and paternal conditions that may be involved in early-life programing of adult NAFLD. First, we describe the maternal nutritional factors that have been suggested to increase the risk of NAFLD in the offspring, such as an obesogenic diet, overweight/obesity, and altered lipogenesis. Second, we review the association of certain vitamin supplementation and the use of some drugs during pregnancy, for instance, glucocorticoids, with a higher risk of NAFLD. Furthermore, we discuss the evidence showing that maternal-fetal pathologies, including gestational diabetes mellitus (GDM), insulin resistance (IR), and intrauterine growth restriction (IUGR), as well as the exposure to environmental contaminants, and the impact of microbiome changes, are important factors in early-life programming of NAFLD. Finally, we review how paternal preconceptional conditions, such as exercise and diet (particularly obesogenic diets), may impact fetal growth and liver function. Altogether, the presented evidence supports the hypothesis that both in utero exposure and parental conditions may influence fetal outcomes, including the development of NAFLD in early life and adulthood. The study of these conditions is crucial to better understand the diverse mechanisms involved in NAFLD, as well as for defining new preventive strategies for this disease.

Birth weight (BW) is an important indicator for newborn health. Both high and low BW is associated with increased risks for adult metabolic diseases. AMPK (AMP-activated protein kinase), mTOR (mechanistic target of rapamycin), and insulin/IGF1 (insulin-like growth factor 1) pathways may function as placental sensors of maternal hormonal and nutritional status. However, the physiological role of these pathways in placenta has not been completely elucidated. To evaluate expression and activation of AMPK, mTOR, and insulin/IGF1 pathways and its association with placental weight (PW), BW, and maternal hormonal and metabolic status, we performed a cross-sectional study in placentas from non-obese mothers with SGA (n = 17), AGA (n = 19) and LGA (n = 10) newborns. We analyzed placental expression of total and phosphorylated key proteins from the AMPK, mTOR and insulin/IGF1 pathways. Maternal and cord blood hormones were determined by ELISA. AMPK and LKB1 activation correlated negatively with PW and BW, cord leptin, and pregestational BMI. Placental SIRT1 inversely correlated with BW, cord leptin, neonatal HOMA-IR, and maternal IGF1. PGC1α correlated negatively with PW and BW. Phosphorylated mTOR positively correlated with maternal glucose, PW and BW. IGF1R was lower in SGA. No changes in p-IGF1R, INSRb, total AKT or p-AKT were found, and pPDK1 was lower in SGA and LGA. These results suggest that placental AMPK, insulin/IGF1, and mTOR pathways may influence fetal growth, perhaps regulating placental physiology, even in metabolically healthy pregnancies. Our study highlights these nutrient sensing pathways as potential molecular mechanisms modulating placental adaptations and, thus, long-term metabolic health.

RAGE is a multi-ligand transmembrane glycoprotein that promotes biological signals associated with inflammatory responses and degenerative diseases. sRAGE is a soluble variant that has been proposed as an inhibitor of RAGE activity. The −374 T/A and −429 T/C polymorphisms of the advanced glycation end-product receptor AGER gene have been associated with the development of some diseases, such as types of cancer, cardiovascular disease, and micro- and macro-vascular disease in diabetes, among others, but their role in metabolic syndrome (MS) is still unknown. We studied 80 healthy males without MS, and 80 males with MS, according to the harmonized criteria. The −374 T/A and −429 T/C polymorphisms were genotyped by RT-PCR, and sRAGE was measured by ELISA. Allelic and genotypic frequencies did not differ between the non-MS and MS groups (−374 T/A p = 0.48, p = 0.57 and −429 T/C p = 0.36, p = 0.59, respectively). Significant differences were found in fasting glucose levels and diastolic blood pressure in the genotypes of the −374 T/A polymorphism in the non-MS group (p < 0.01 and p = 0.008). Glucose levels were different in the −429 T/C genotypes in the MS group (p = 0.02). The sRAGE levels were similar in both groups, but the non-MS group showed a significant difference between individuals with only 1 or 2 components of metabolic syndrome (p = 0.047). However, no associations of any SNP with MS were found (recessive model p = 0.48, dominant model p = 0.82 for −374 T/A; recessive model p = 0.48, dominant model p = 0.42 for −429 T/C). The −374 T/A and −429 T/C polymorphisms were not associated with MS in a Mexican population and had no influence on serum sRAGE levels.

Background: Metabolic dysfunction-associated steatotic liver disease (MALSD) is defined as the excessive accumulation of triglycerides in the liver in the presence of at least one cardiometabolic risk factor and liver biopsy remains the diagnostic gold standard. This study aimed to evaluate the diagnostic performance of adiposity and metabolism related indices for the non-invasive detection of MASLD and the metabolic dysfunction-associated steatohepatitis (MASH). Methods: A cross-sectional study was conducted in 161 Mexican adults undergoing laparoscopic cholecystectomy, during which liver biopsies were obtained for histological evaluation. Indices such as the Hepatic Steatosis Index (HSI), the Triglyceride–Glucose index (TyG), TyG-BMI (TyG adjusted for body mass index), and TyG-WC (TyG adjusted for waist circumference), among others, were calculated. Results: Of the 161 participants, 66 were diagnosed with MASLD, and 50 of them had histological evidence of MASH. All adiposity and metabolic indices evaluated were significantly higher in MASLD patients compared with controls. Logistic regression identified HSI, TyG, TyG-BMI, and TyG-WC as independently associated with MASLD and MASH, with TyG showing the strongest association. Correlation analyses demonstrated that TyG-BMI and TyG-WC were most strongly associated with histological features of MASH. Receiver operating characteristic curve analyses showed that TyG-WC had the highest diagnostic accuracy for MASLD (AUC 0.721, 95% CI 0.641–0.802) and MASH (AUC 0.735, 95% CI 0.648–0.823), while TyG-BMI displayed high sensitivity (0.758 for MASLD; 0.780 for MASH). Conclusions: Triglyceride–glucose-based indices, particularly TyG-WC and TyG-BMI, showed the highest diagnostic performance for detecting MASLD and MASH, suggesting that these indices may serve as practical, non-invasive tools for identifying individuals at risk.