Alejandra Espinosa

Mitochondria are a key organelle in maintaining metabolic homeostasis. It not only generates most of the cell’s energy through oxidative phosphorylation but also acts as a complex sensor of the redox state and oxygen in the cell. This review thoroughly analyzes the interactions among mitochondrial iron metabolism, mitochondrial reactive oxygen species (mtROS), and lipid peroxidation (LPO), the triggering factors of ferroptosis, an iron-dependent form of programmed cell death. We point out research showing that intrinsic mitochondrial machinery, such as iron–sulfur (Fe-S) cluster assembly and heme metabolism, is both an important cofactor and a master regulator. If these processes are disrupted, they can lead to ferroptosis. Unlike views that focus on the cytosol, we explain that the stability of Fe-S clusters in complexes such as aconitase and respiratory Complex I is crucial for preventing electron leakage and excessive mtROS formation. The Fenton reaction and its direct effect on cardiolipin (CL) oxidation in the inner membrane of mitochondria is a central event in cardiometabolic diseases. Its peroxidation and breakdown make the organelle very unstable and lead to cell death though Ca²⁺ overload and a significantly decreased reduced/oxidized glutathione ratio. Additionally, the functions of essential iron transporters and glutathione homeostasis are examined, and their dysregulation is correlated with ferroptosis-associated progression of cardiometabolic and neurodegenerative disorders, such as obesity and Alzheimer’s disease. This review focused on the need to revisit the classic bioenergetic core of the mitochondria as a key player in the pathophysiology of metabolic and neurodegenerative diseases.

Recent developments have highlighted the importance of using by-products such as brewer’s spent grain (BSG) as functional food ingredients. BSG is a source of polyphenols, antioxidants, dietary fiber, and protein, all of which are crucial for preventing metabolic syndrome and cardiovascular disease. This review focuses on bioactive compounds in BSG, such as ferulic and p-coumaric acids, which are distinguished for their antioxidant and anti-inflammatory properties. These compounds play a vital role in liver protection by boosting antioxidant enzyme activity and reducing inflammation and oxidative stress. Additionally, arabinoxylans (AX) in BSG enhance gut health by promoting the growth of beneficial microbiota. The review also identifies gaps in understanding how processing affects bioactive compound bioavailability in foods, emphasizing the need for innovative food technologies to enhance nutrient release and absorption, including the recent studies that show the role of gut microbiota in fermenting BSG components, leading to the release of beneficial compounds, such as ferulic and butyric, which positively influence health and metabolism. Despite these advancements, further research is essential to explore the interactions within the gut, liver effects, and the overall health benefits of BSG, aiming to optimize processing techniques to preserve its nutritional value and promote sustainable food innovation.

Mitochondria are a key organelle in maintaining metabolic homeostasis. It not only generates most of the cell's energy through oxidative phosphorylation but also acts as a complex sensor of the redox state and oxygen in the cell. This review thoroughly ana-lyzes the interactions among mitochondrial iron metabolism, mitochondrial reactive oxygen species (mtROS), and lipid peroxidation (LPO), the triggering factors of fer-roptosis, an iron-dependent form of programmed cell death. We point out research showing that intrinsic mitochondrial machinery, such as iron-sulfur (Fe-S) cluster as-sembly and heme metabolism, is both an important cofactor and a master regulator. If these processes are disrupted, they can lead to ferroptosis. Unlike views that focus on the cytosol, we explain that the stability of Fe-S clusters in complexes such as aconitase and respiratory Complex I is crucial for preventing electron leakage and excessive mtROS formation. The Fenton reaction and its direct effect on cardiolipin (CL) oxidation in the inner membrane of mitochondria is a central event in cardiometabolic diseases. Its peroxidation and breakdown make the organelle very unstable and lead to cell death though Ca2+ overload and a significantly decreased reduced/oxidized glutathione ratio. Additionally, the functions of essential iron transporters and glutathione homeostasis are examined, and their dysregulation is correlated with ferroptosis-associated pro-gression of cardiometabolic and neurodegenerative disorders, such as obesity and Alzheimer’s disease. This review focused on the need to revisit the classic bioenergetic core of the mitochondria as a key player in the pathophysiology of metabolic and neu-rodegenerative diseases.

El estrés es uno de los fenómenos más notorios en la actualidad y en tanto se torna crónico afecta la salud de las personas en múltiples niveles. El estrés académico afecta a los estudiantes universitarios durante su proceso de formación, repercutiendo en su calidad de vida. Existen pocos estudios en Chile que examinen la relación entre el estrés fisiológico crónico y las diferentes dimensiones del estrés psicológico. Objetivo: evaluar la relación entre los niveles de cortisol en pelo y la autopercepción psicológica frente al estrés. Sujetos y métodos: En una muestra de 38 estudiantes de la Facultad de Medicina de la Universidad de Chile se evaluó el estrés crónico mediante la medición de cortisol en pelo y se registró la autopercepción del estrés mediante la aplicación del cuestionario de percepción global de estado (CPGE). Los resultados se analizaron utilizando estadística descriptiva y la prueba no paramétrica U de Wilcoxon-Mann-Whitney. Resultados: 34% de los estudiantes presentaron niveles altos de cortisol en pelo, además se encontró asociación entre cortisol y la memoria para sujetos femeninos, así como entre el cortisol y la dimensión “síntomas físicos” del CPGE para sujetos masculinos. Conclusión: Este estudio demuestra una acotada asociación entre el estrés percibido y el cortisol en pelo, mostrando que muchos indicadores de estrés psicológico no se correlacionan necesariamente con niveles altos de cortisol y por lo tanto estos síntomas debieran tratarse independientemente, mientras que las manifestaciones psicológicas asociadas a los altos niveles de cortisol podrían utilizarse como indicadores de estrés fisiológico.

Bioactive compounds have shown significant potential in the management of obesity and metabolic syndrome (MetS). This study investigates the effects of antioxidant lipids (ALω-3), synthetized through enzymatic acidolysis using non-specific lipase B from Candida antarctica under supercritical CO₂ conditions. These lipids were derived from a concentrate of rainbow trout (Oncorhynchus mykiss) belly oil, rich in long-chain polyunsaturated omega-3 fatty acids (LCPUFAn-3), and cold-pressed maqui seed oil (MO, Aristotelia chilensis (Mol.) Stuntz). Their effects were then evaluated in a murine high-fat diet (HFD) model. The fatty acid profile, tocopherol and tocotrienol content, and thin-layer chromatography of ALω-3 were analyzed. After 8 weeks on an HFD, male C57BL/6 mice were divided into four groups and switched to a control diet (CD) with the following supplements for 3 weeks: Glycerol (G), commercial marine Omega-3 (CMω-3), a mixture of LCPUFAn-3 concentrate + MO (Mω-3), or ALω-3. The total body and organ weights, serum markers, and liver and visceral fat pro-inflammatory marker expression levels were assessed. ALω-3 contained 13.4% oleic, 33.9% linoleic, 6.3% α-linolenic, 10.7% eicosapentaenoic, and 16.2% docosahexaenoic fatty acids. The β, γ, δ-tocopherol, and β, γ-tocotrienol values were 22.9 ± 1.4, 24.9 ± 0.2, 6.8 ± 0.7, 22.9 ± 1.7, and 22.4 ± 4.7 mg·kg⁻¹, respectively, with α-tocopherol detected in traces. ALω-3 supplementation increased serum Trolox equivalent capacity, significantly reduced serum GPT levels (p < 0.01), and enhanced postprandial glucose tolerance (p < 0.001), although it did not alter insulin resistance (HOMA-IR). These findings indicate ALω-3′s potential for mitigating the glucose intolerance, liver damage, and oxidative stress associated with obesity and MetS, highlighting the need for additional research to explore its potential health benefits.

Background/Objectives: This study investigates the effects of a high-fat diet (HFD) during pregnancy and lactation on maternal and offspring health, focusing on behavioral, metabolic, and fatty acid composition outcomes in a rat model. Methods: Twelve female Sprague–Dawley rats were fed either a control diet, CD (n = 6), or HFD (n = 6) for 12 weeks, encompassing mating, gestation, and lactation periods (18 weeks). Anxiety-like behavior, maternal behavior, depression-like behavior, and social play were studied. Post mortem, the liver function, hepatic steatosis, and fatty acid composition (erythrocytes, liver, adipose tissue) were evaluated. In regard to desaturase enzymes (Δ-6D and Δ-5D), liver activity, protein mass, and gene expression (RT-PCR) were analyzed. Additionally, gene expression of PPAR-α, ACOX, CPT1-α, SREBP-1c, ACC, and FAS was assessed. Statistical analysis was performed using Student’s t-test, mean ± SD (p < 0.05). Results: The HFD significantly increased maternal weight and anxiety-like behavior while reducing social interactions exclusively in male offspring (p < 0.05). It also led to a significant decrease in the synthesis and content of n-3 PUFAs in the analyzed tissues, induced hepatic steatosis, and upregulated the expression of pro-lipogenic genes in the maternal liver. Conclusions: These findings suggest that long-term HFD consumption alters tissue fatty acid composition, disrupts metabolic homeostasis, and contributes to behavioral changes, increasing anxiety-like behaviors in pregnant dams and reducing social interactions in male offspring. Overall, this study provides further insight into the detrimental effects of HFD consumption during the perinatal period.

A new antioxidant lipid (AL) was synthesized from rainbow trout (Oncorhynchus mykiss) belly oil and cold-pressed maqui (CPM) (Aristotelia chilensis (Mol.) Stuntz) seed oil via enzymatic interesterification using Thermomyces lanuginosus in supercritical CO₂ medium. A Box–Behnken design with 15 experiments was employed, with the independent variables being the following: belly oil/CPM oil ratio (10/90, 50/50, and 90/10, w/w), supercritical CO₂ temperature (40.0, 50.0, and 60.0 °C), and supercritical CO₂ pressure (100.0, 200.0, and 300.0 bar) for enzymatic interesterification. A multiple optimization was conducted based on the response variables yield and eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and tocopherol contents. The optimized conditions for the AL synthesis were: 81.4/18.6 (w/w), 40.0 °C and 299.99 bar, respectively. The corresponding responses variables were: 77.10% for yield, 5.12 and 4.95 g·100 g⁻¹ total fatty acids for EPA and DHA, respectively, and 217.96, 4.28, 3.48, 64.48, and 6.39 mg·kg⁻¹ oil for α-tocopherol, α-tocotrienol, β-tocopherol, γ-tocopherol, and δ-tocopherol, respectively. A novel AL was successfully synthesized starting from two abundant natural resources commonly considered as by-products during industrial processing. In agreement with the high EPA, DHA, and tocopherol presence, this AL can be recommended to be employed in nutritional and therapeutic supplements, according to its health benefits, particularly concerning antioxidant and anti-inflammatory properties.

This study evaluated the effects of cold-pressed maqui (Aristotelia chilensis (Mol.) Stuntz) seed oil (MO) on liver metabolism and biochemical markers in a high-fat diet (HFD) murine model. In it, the fatty acid profile, tocopherol and tocotrienol contents, and antioxidant capacity of MO were analyzed. Male C57BL/6 mice were divided into four groups (i.e., a, b, c, and d groups) and supplemented for 12 weeks according to the following distribution: (a) control diet (CD)-sunflower oil (SO), (b) CD+MO, (c) HFD+SO, and (d) HFD+MO. Total body and organ weights, serum markers, and liver fat infiltration were assessed. MO contained 32.31% oleic acid, 46.41% linoleic acid, and 10.83% α-linolenic acid; additionally, α- and γ-tocopherol levels were 339.09 ± 5.15 and 135.52 ± 38.03 mg/kg, respectively, while β-, δ-tocopherol, and α-tocotrienol were present in trace amounts and the antioxidant capacity measured was 6.66 ± 0.19 μmol Trolox equivalent/g. MO supplementation significantly reduced the visceral fat (0.76 ± 0.06 g vs. 1.32 ± 0.04 g) and GPT (glutamate pyruvate transaminase) levels (71.8 ± 5.0 vs. 35.2 ± 2.6 U/L), and the liver fat infiltration score (6 vs. 3) in the HFD+MO group compared to HFD+SO. It is suggested that MO may effectively prevent fatty liver disease, warranting further research on its potential benefits for human health.

Myokines, bioactive peptides released by skeletal muscle, have emerged as crucial regulators of metabolic and protective pathways in peripheral tissues, particularly in combating oxidative stress and inflammation. Their plasma concentration significantly increases following exercise, offering valuable insights into the role of physical activity in preventing sarcopenia and mitigating metabolic diseases, including obesity, diabetes, and metabolic dysfunction-associated steatotic liver disease (MASLD). This review focuses on discussing the roles of specific myokines in activating intracellular signaling pathways within the liver, which confer protection against steatosis and lipid peroxidation. We detail the mechanism underlying lipid peroxidation and highlight the liver’s antioxidant defenses, such as glutathione (GSH) and glutathione peroxidase 4 (GPX4), which are pivotal in reducing ferroptosis. Furthermore, we provide an in-depth analysis of key myokines, including myostatin, brain-derived neurotrophic factor (BDNF), and irisin, among others, and their potential impact on liver function. Finally, we discuss the molecular mechanisms through which these myokines influence oxidate stress and lipid metabolism, emphasizing their capacity to modulate antioxidant responses in the liver. Finally, we underscore the therapeutic potential of exercise as a non-pharmacological intervention to enhance myokine release, thereby preventing the progression of MASD through improved hepatic antioxidant defenses. This review represents a comprehensive perspective on the intersection of exercise, myokine biology, and liver health.

Myokines are peptides released by the skeletal muscle that exert effects on peripheral tissues, activating metabolic or protective pathways against oxidative stress and inflammation. Many myokines increase their plasma levels after exercise, providing new insights into the role of physical activity in combating sarcopenia and preventing metabolic diseases, such as obesity, diabetes, and metabolic dysfunction associated with steatotic liver disease (MASLD). This review aims to discuss the roles of specific myokines in activating intracellular pathways in the liver to protect against steatosis and lipoperoxidation in MASLD. The progression of liver disease from steatosis to cirrhosis is partially driven by ferroptosis, an iron-dependent form of cell death linked to oxidative stress and lipoperoxidation. Exercise-induced myokines, such as irisin, have been shown to upregulate antioxidant enzymes such as glutathione (GSH) and glutathione peroxidase 4 (GPX4), which are crucial in reducing ferroptosis in hepatic tissues. This review provides a comprehensive perspective on the protective effects of myokines in the liver, particularly against lipid peroxidation and ferroptosis in MASLD, and highlights exercise as a therapeutic strategy to prevent the progression of this liver pathology.