Emerging models for studying adipose tissue metabolism.

Understanding adipose metabolism is essential for addressing obesity and related health concerns. However, the ethical and scientific pressure to animal testing, aligning with the 3Rs, has triggered the implementation of diverse alternative models for analysing anomalies in adipose metabolism. In this review, we will address this issue from various perspectives. Traditional adipocyte cell cultures, whether animal or human-derived, offer a fundamental starting point. These systems have their merits but may not fully replicate in vivo complexity. Established cell lines are valuable for high-throughput screening but may lack the authenticity of primary-derived adipocytes, which closely mimic native tissue. To enhance model sophistication, spheroids have been introduced. These three-dimensional cultures better mimicking the in vivo microenvironment, enabling the study of intricate cell-cell interactions, gene expression, and metabolic pathways. Organ-on-a-chip (OoC) platforms take this further by integrating multiple cell types into microfluidic devices, simulating tissue-level functions. Adipose-OoC (AOoC) provides dynamic environments with applications spanning drug testing to personalized medicine and nutrition. Beyond in vitro models, genetically amenable organisms (Caenorhabditis elegans, Drosophila melanogaster, and zebrafish larvae) have become powerful tools for investigating fundamental molecular mechanisms that govern adipose tissue functions. Their genetic tractability allows for efficient manipulation and high-throughput studies. In conclusion, a diverse array of research models is crucial for deciphering adipose metabolism. By leveraging traditional adipocyte cell cultures, primary-derived cells, spheroids, AOoCs, and lower organism models, we bridge the gap between animal testing and a more ethical, scientifically robust, and human-relevant approach, advancing our understanding of adipose tissue metabolism and its impact on health.

Exploring the Relationship between Diamine Oxidase and Psychotropic Medications in Fibromyalgia Treatment, Finding No Reduction in Diamine Oxidase Levels and Activity except with Citalopram.

Background: Histamine intolerance manifests when there is an imbalance between the production of histamine and the body's capacity to metabolise it. Within the gastrointestinal tract, diamine oxidase (DAO) plays a pivotal role in breaking down ingested histamine. Insufficient levels of DAO have been linked to various diseases affecting the respiratory, cardiovascular, nervous, muscular, and digestive systems; some of these symptoms are evidenced in fibromyalgia syndrome. This underscores the crucial role of DAO in maintaining the histamine balance and highlights its association with diverse physiological systems and health conditions. The management of fibromyalgia commonly involves the use of psychotropic medications; however, their potential interactions with DAO remain not fully elucidated. Methods: This study delved into the influence of various psychotropic medications on DAO activity through in vitro experiments. Additionally, we explored their impact on the human intestinal cell line Caco-2, examining alterations in DAO expression at both the mRNA and protein levels along with DAO activity. Results: Notably, the examined drugs-sertraline, pregabalin, paroxetine, alprazolam, and lorazepam-did not exhibit inhibitory effects on DAO activity or lead to reductions in DAO levels. In contrast, citalopram demonstrated a decrease in DAO activity in in vitro assays without influencing DAO levels and activity in human enterocytes. Conclusions: These findings imply that a collaborative approach involving psychotropic medications and DAO enzyme supplementation for individuals with fibromyalgia and a DAO deficiency could offer potential benefits for healthcare professionals in their routine clinical practice.

Diamine Oxidase Interactions with Anti-Inflammatory and Anti-Migraine Medicines in the Treatment of Migraine.

Histamine intolerance arises when there is a disparity between the production of histamine and the body's ability to break it down. In the gastrointestinal tract, the primary enzyme responsible for metabolizing ingested histamine is diamine oxidase (DAO), and a shortage of this enzyme has been associated with some diseases related to the respiratory, cardiovascular, nervous, muscular, and digestive systems, in addition to migraines. The treatment of migraines typically revolves around the utilization of both anti-migraine and anti-inflammatory drugs, but their interaction with DAO is not thoroughly understood. In this study, we examined the impact of nonsteroidal anti-inflammatory drugs (NSAIDs) and anti-migraine medications on DAO activity through in vitro experiments. We also investigated their effects on the human intestinal cell line Caco-2, assessing changes in DAO expression (both at the mRNA and protein levels) as well as DAO activity. The tested drugs, including ibuprofen, acetylsalicylic acid, paracetamol, a combination of acetylsalicylic acid with paracetamol and caffeine, zolmitriptan, and sumatriptan, did not inhibit DAO activity or reduce their levels. However, naproxen reduced DAO protein levels in human enterocyte cultures while not affecting DAO activity. These results suggest that combining anti-inflammatory and anti-migraine drugs with DAO enzyme supplementation for migraine patients with DAO deficiency could be beneficial for healthcare professionals in their daily practice.

Potential therapeutic implications of histidine catabolism by the gut microbiota in NAFLD patients with morbid obesity.

The gut microbiota contributes to the pathophysiology of non-alcoholic fatty liver disease (NAFLD). Histidine is a key energy source for the microbiota, scavenging it from the host. Its role in NAFLD is poorly known. Plasma metabolomics, liver transcriptomics, and fecal metagenomics were performed in three human cohorts coupled with hepatocyte, rodent, and Drosophila models. Machine learning analyses identified plasma histidine as being strongly inversely associated with steatosis and linked to a hepatic transcriptomic signature involved in insulin signaling, inflammation, and trace amine-associated receptor 1. Circulating histidine was inversely associated with Proteobacteria and positively with bacteria lacking the histidine utilization (Hut) system. Histidine supplementation improved NAFLD in different animal models (diet-induced NAFLD in mouse and flies, ob/ob mouse, and ovariectomized rats) and reduced de novo lipogenesis. Fecal microbiota transplantation (FMT) from low-histidine donors and mono-colonization of germ-free flies with Enterobacter cloacae increased triglyceride accumulation and reduced histidine content. The interplay among microbiota, histidine catabolism, and NAFLD opens therapeutic opportunities.

Preventive Treatment with Astaxanthin Microencapsulated with Spirulina Powder, Administered in a Dose Range Equivalent to Human Consumption, Prevents LPS-Induced Cognitive Impairment in Rats.

Cognitive alterations are a common feature associated with many neurodegenerative diseases and are considered a major health concern worldwide. Cognitive alterations are triggered by microglia activation and oxidative/inflammatory processes in specific areas of the central nervous system. Consumption of bioactive compounds with antioxidative and anti-inflammatory effects, such as astaxanthin and spirulina, can help in preventing the development of these pathologies. In this study, we have investigated the potential beneficial neuroprotective effects of a low dose of astaxanthin (ASX) microencapsulated within spirulina (ASXSP) in female rats to prevent the cognitive deficits associated with the administration of LPS. Alterations in memory processing were evaluated in the Y-Maze and Morris Water Maze (MWM) paradigms. Changes in microglia activation and in gut microbiota content were also investigated. Our results demonstrate that LPS modified long-term memory in the MWM and increased microglia activation in the hippocampus and prefrontal cortex. Preventive treatment with ASXSP ameliorated LPS-cognitive alterations and microglia activation in both brain regions. Moreover, ASXSP was able to partially revert LPS-induced gut dysbiosis. Our results demonstrate the neuroprotective benefits of ASX when microencapsulated with spirulina acting through different mechanisms, including antioxidant, anti-inflammatory and, probably, prebiotic actions.

Interaction of Diamine Oxidase with Psychostimulant Drugs for ADHD Management.

Histamine intolerance occurs when there is an imbalance between histamine production and the capacity for histamine degradation. Diamine oxidase (DAO) is the main enzyme for the catabolism of ingested histamine degradation in the gastrointestinal tract and its deficiency has been linked to allergy-like symptoms. Psychostimulant drugs are commonly used to treat Attention Deficit Hyperactivity Disorder (ADHD), but their interaction with DAO is not well characterized. In this work, we evaluated the effects of psychostimulant drugs (methylphenidate and lisdexamfetamine) on in vitro DAO activity and in the human cell line of enterocytes (Caco-2), evaluating DAO expression (mRNA and protein) and DAO activity. Methylphenidate and lisdexamfetamine did not repress the in vitro DAO activity. In addition, in Caco-2 cells, lisdexamfetamine promoted a strong upregulation of DAO mRNA levels, whereas methylphenidate tended to induce DAO activity. To sum up, methylphenidate and lisdexamfetamine treatments do not reduce DAO activity. These findings could be useful for physicians prescribing these two drugs to ADHD patients affected by DAO deficiency.

Vitis vinifera L. Bioactive Components Modulate Adipose Tissue Metabolic Markers of Healthy Rats in a Photoperiod-Dependent Manner.

SCOPE: The beneficial health effects of (poly)phenol-rich foods such as red grapes mainly depend on both the type and concentration of (poly)phenols. Since fruit (poly)phenol content is influenced by growing conditions, the study examines the seasonal effects of red grapes (Vitis vinifera L.), grown under various cultivation conditions, on metabolic markers of adipose tissue in healthy rats. METHODS AND RESULTS: For this purpose, Fischer 344 rats are exposed into three different light-dark cycles and daily supplemented with 100 mg kg-1 of either conventionally or organically grown red grapes for 10 weeks (n = 6). Seasonal consumption of organic grapes (OGs), which are richer in anthocyanins, increases energy expenditure (EE) of animals exposed to long photoperiod and enhances uncoupling protein 1 (UCP1) protein expression in brown adipose tissue of animals under standard photoperiod. Additionally, red grape consumption affects the gene expression profile of white adipose tissue (WAT), upregulating browning markers of subcutaneous WAT in 12 h light (L12) and 18 h light (L18) photoperiods, and downregulating adipogenic and lipolytic markers of visceral WAT in 6 h light (L6) and L12 photoperiods. CONCLUSIONS: These results clearly show that bioactive compounds of grapes can modulate the metabolic markers of white and brown adipose tissues in a photoperiod and depot-dependent manner, partly affecting EE when consumed out of season.

Maresin 1 activates brown adipose tissue and promotes browning of white adipose tissue in mice.

OBJECTIVE: Maresin 1 (MaR1) is a docosahexaenoic acid-derived proresolving lipid mediator with insulin-sensitizing and anti-steatosis properties. Here, we aim to unravel MaR1 actions on brown adipose tissue (BAT) activation and white adipose tissue (WAT) browning. METHODS: MaR1 actions were tested in cultured murine brown adipocytes and in human mesenchymal stem cells (hMSC)-derived adipocytes. In vivo effects of MaR1 were tested in diet-induced obese (DIO) mice and lean WT and Il6 knockout (Il6-/-) mice. RESULTS: In cultured differentiated murine brown adipocytes, MaR1 reduces the expression of inflammatory genes, while stimulates glucose uptake, fatty acid utilization and oxygen consumption rate, along with the upregulation of mitochondrial mass and genes involved in mitochondrial biogenesis and function and the thermogenic program. In Leucine Rich Repeat Containing G Protein-Coupled Receptor 6 (LGR6)-depleted brown adipocytes using siRNA, the stimulatory effect of MaR1 on thermogenic genes was abrogated. In DIO mice, MaR1 promotes BAT remodeling, characterized by higher expression of genes encoding for master regulators of mitochondrial biogenesis and function and iBAT thermogenic activation, together with increased M2 macrophage markers. In addition, MaR1-treated DIO mice exhibit a better response to cold-induced BAT activation. Moreover, MaR1 induces a beige adipocyte signature in inguinal WAT of DIO mice and in hMSC-derived adipocytes. MaR1 potentiates Il6 expression in brown adipocytes and BAT of cold exposed lean WT mice. Interestingly, the thermogenic properties of MaR1 were abrogated in Il6-/- mice. CONCLUSIONS: These data reveal MaR1 as a novel agent that promotes BAT activation and WAT browning by regulating thermogenic program in adipocytes and M2 polarization of macrophages. Moreover, our data suggest that LGR6 receptor is mediating MaR1 actions on brown adipocytes, and that IL-6 is required for the thermogenic effects of MaR1.

Omics biomarkers and an approach for their practical implementation to delineate health status for personalized nutrition strategies.

Personalized nutrition (PN) has gained much attention as a tool for empowerment of consumers to promote changes in dietary behavior, optimizing health status and preventing diet related diseases. Generalized implementation of PN faces different obstacles, one of the most relevant being metabolic characterization of the individual. Although omics technologies allow for assessment the dynamics of metabolism with unprecedented detail, its translatability as affordable and simple PN protocols is still difficult due to the complexity of metabolic regulation and to different technical and economical constrains. In this work, we propose a conceptual framework that considers the dysregulation of a few overarching processes, namely Carbohydrate metabolism, lipid metabolism, inflammation, oxidative stress and microbiota-derived metabolites, as the basis of the onset of several non-communicable diseases. These processes can be assessed and characterized by specific sets of proteomic, metabolomic and genetic markers that minimize operational constrains and maximize the information obtained at the individual level. Current machine learning and data analysis methodologies allow the development of algorithms to integrate omics and genetic markers. Reduction of dimensionality of variables facilitates the implementation of omics and genetic information in digital tools. This framework is exemplified by presenting the EU-Funded project PREVENTOMICS as a use case.

Single and Joined Behaviour of Circulating Biomarkers and Metabolic Parameters in High-Fit and Low-Fit Healthy Females.

Biomarkers are important in the assessment of health and disease, but are poorly studied in still healthy individuals with a (potential) different risk for metabolic disease. This study investigated, first, how single biomarkers and metabolic parameters, functional biomarker and metabolic parameter categories, and total biomarker and metabolic parameter profiles behave in young healthy female adults of different aerobic fitness and, second, how these biomarkers and metabolic parameters are affected by recent exercise in these healthy individuals. A total of 102 biomarkers and metabolic parameters were analysed in serum or plasma samples from 30 young, healthy, female adults divided into a high-fit (V̇O2peak ≥ 47 mL/kg/min, N = 15) and a low-fit (V̇O2peak ≤ 37 mL/kg/min, N = 15) group, at baseline and overnight after a single bout of exercise (60 min, 70% V̇O2peak). Our results show that total biomarker and metabolic parameter profiles were similar between high-fit and low-fit females. Recent exercise significantly affected several single biomarkers and metabolic parameters, mostly related to inflammation and lipid metabolism. Furthermore, functional biomarker and metabolic parameter categories corresponded to biomarker and metabolic parameter clusters generated via hierarchical clustering models. In conclusion, this study provides insight into the single and joined behavior of circulating biomarkers and metabolic parameters in healthy females, and identified functional biomarker and metabolic parameter categories that may be used for the characterisation of human health physiology.

p27Kip1 Deficiency Impairs Brown Adipose Tissue Function Favouring Fat Accumulation in Mice.

The aim of this work was to investigate the effect of the whole-body deletion of p27 on the activity of brown adipose tissue and the susceptibility to develop obesity and glucose homeostasis disturbances in mice, especially when subjected to a high fat diet. p27 knockout (p27-/-) and wild type (WT) mice were fed a normal chow diet or a high fat diet (HFD) for 10-weeks. Body weight and composition were assessed. Insulin and glucose tolerance tests and indirect calorimetry assays were performed. Histological analysis of interscapular BAT (iBAT) was carried out, and expression of key genes/proteins involved in BAT function were characterized by qPCR and Western blot. iBAT activity was estimated by 18F-fluorodeoxyglucose (18FDG) uptake with microPET. p27-/- mice were more prone to develop obesity and insulin resistance, exhibiting increased size of all fat depots. p27-/- mice displayed a higher respiratory exchange ratio. iBAT presented larger adipocytes in p27-/- HFD mice, accompanied by downregulation of both Glut1 and uncoupling protein 1 (UCP1) in parallel with defective insulin signalling. Moreover, p27-/- HFD mice exhibited impaired response to cold exposure, characterized by a reduced iBAT 18FDG uptake and difficulty to maintain body temperature when exposed to cold compared to WT HFD mice, suggesting reduced thermogenic capacity. These data suggest that p27 could play a role in BAT activation and in the susceptibility to develop obesity and insulin resistance.

Reduction of Obesity and Insulin Resistance through Dual Targeting of VAT and BAT by a Novel Combination of Metabolic Cofactors.

Obesity is an epidemic disease worldwide, characterized by excessive fat accumulation associated with several metabolic perturbations, such as metabolic syndrome, insulin resistance, hypertension, and dyslipidemia. To improve this situation, a specific combination of metabolic cofactors (MC) (betaine, N-acetylcysteine, L-carnitine, and nicotinamide riboside) was assessed as a promising treatment in a high-fat diet (HFD) mouse model. Obese animals were distributed into two groups, orally treated with the vehicle (obese + vehicle) or with the combination of metabolic cofactors (obese + MC) for 4 weeks. Body and adipose depots weights; insulin and glucose tolerance tests; indirect calorimetry; and thermography assays were performed at the end of the intervention. Histological analysis of epidydimal white adipose tissue (EWAT) and brown adipose tissue (BAT) was carried out, and the expression of key genes involved in both fat depots was characterized by qPCR. We demonstrated that MC supplementation conferred a moderate reduction of obesity and adiposity, an improvement in serum glucose and lipid metabolic parameters, an important improvement in lipid oxidation, and a decrease in adipocyte hypertrophy. Moreover, MC-treated animals presented increased adipose gene expression in EWAT related to lipolysis and fatty acid oxidation. Furthermore, MC supplementation reduced glucose intolerance and insulin resistance, with an increased expression of the glucose transporter Glut4; and decreased fat accumulation in BAT, raising non-shivering thermogenesis. This treatment based on a specific combination of metabolic cofactors mitigates important pathophysiological characteristics of obesity, representing a promising clinical approach to this metabolic disease.

Microbiota Dysbiosis and Gut Barrier Dysfunction Associated with Non-Alcoholic Fatty Liver Disease Are Modulated by a Specific Metabolic Cofactors' Combination.

The gut is a selective barrier that not only allows the translocation of nutrients from food, but also microbe-derived metabolites to the systemic circulation that flows through the liver. Microbiota dysbiosis occurs when energy imbalances appear due to an unhealthy diet and a sedentary lifestyle. Dysbiosis has a critical impact on increasing intestinal permeability and epithelial barrier deterioration, contributing to bacterial and antigen translocation to the liver, triggering non-alcoholic fatty liver disease (NAFLD) progression. In this study, the potential therapeutic/beneficial effects of a combination of metabolic cofactors (a multi-ingredient; MI) (betaine, N-acetylcysteine, L-carnitine, and nicotinamide riboside) against NAFLD were evaluated. In addition, we investigated the effects of this metabolic cofactors' combination as a modulator of other players of the gut-liver axis during the disease, including gut barrier dysfunction and microbiota dysbiosis. Diet-induced NAFLD mice were distributed into two groups, treated with the vehicle (NAFLD group) or with a combination of metabolic cofactors (NAFLD-MI group), and small intestines were harvested from all animals for histological, molecular, and omics analysis. The MI treatment ameliorated gut morphological changes, decreased gut barrier permeability, and reduced gene expression of some proinflammatory cytokines. Moreover, epithelial cell proliferation and the number of goblet cells were increased after MI supplementation. In addition, supplementation with the MI combination promoted changes in the intestinal microbiota composition and diversity, as well as modulating short-chain fatty acids (SCFAs) concentrations in feces. Taken together, this specific combination of metabolic cofactors can reverse gut barrier disruption and microbiota dysbiosis contributing to the amelioration of NAFLD progression by modulating key players of the gut-liver axis.

The Catalan Surveillance Network of SARS-CoV-2 in Sewage: design, implementation, and performance.

Wastewater-based epidemiology has shown to be an efficient tool to track the circulation of SARS-CoV-2 in communities assisted by wastewater treatment plants (WWTPs). The challenge comes when this approach is employed to help Health authorities in their decision-making. Here, we describe the roadmap for the design and deployment of SARSAIGUA, the Catalan Surveillance Network of SARS-CoV-2 in Sewage. The network monitors, weekly or biweekly, 56 WWTPs evenly distributed across the territory and serving 6 M inhabitants (80% of the Catalan population). Each week, samples from 45 WWTPs are collected, analyzed, results reported to Health authorities, and finally published within less than 72 h in an online dashboard ( https://sarsaigua.icra.cat ). After 20 months of monitoring (July 20-March 22), the standardized viral load (gene copies/day) in all the WWTPs monitored fairly matched the cumulative number of COVID-19 cases along the successive pandemic waves, showing a good fit with the diagnosed cases in the served municipalities (Spearman Rho = 0.69). Here we describe the roadmap of the design and deployment of SARSAIGUA while providing several open-access tools for the management and visualization of the surveillance data.

A double-blinded, randomized, parallel intervention to evaluate biomarker-based nutrition plans for weight loss: The PREVENTOMICS study.

BACKGROUND & AIMS: Growing evidence suggests that biomarker-guided dietary interventions can optimize response to treatment. In this study, we evaluated the efficacy of the PREVENTOMCIS platform-which uses metabolomic and genetic information to classify individuals into different 'metabolic clusters' and create personalized dietary plans-for improving health outcomes in subjects with overweight or obesity. METHODS: A 10-week parallel, double-blinded, randomized intervention was conducted in 100 adults (82 completers) aged 18-65 years, with body mass index ≥27 but <40 kg/m2, who were allocated into either a personalized diet group (n = 49) or a control diet group (n = 51). About 60% of all food was provided free-of-charge. No specific instruction to restrict energy intake was given. The primary outcome was change in fat mass from baseline, evaluated by dual energy X-ray absorptiometry. Other endpoints included body weight, waist circumference, lipid profile, glucose homeostasis markers, inflammatory markers, blood pressure, physical activity, stress and eating behavior. RESULTS: There were significant main effects of time (P < 0.01), but no group main effects, or time-by-group interactions, for the change in fat mass (personalized: -2.1 [95% CI -2.9, -1.4] kg; control: -2.0 [95% CI -2.7, -1.3] kg) and body weight (personalized: -3.1 [95% CI -4.1, -2.1] kg; control: -3.3 [95% CI -4.2, -2.4] kg). The difference between groups in fat mass change was -0.1 kg (95% CI -1.2, 0.9 kg, P = 0.77). Both diets resulted in significant improvements in insulin resistance and lipid profile, but there were no significant differences between groups. CONCLUSION: Personalized dietary plans did not result in greater benefits over a generic, but generally healthy diet, in this 10-week clinical trial. Further studies are required to establish the soundness of different precision nutrition approaches, and translate this science into clinically relevant dietary advice to reduce the burden of obesity and its comorbidities. CLINICAL TRIAL REGISTRY: ClinicalTrials.gov registry (NCT04590989).

Proanthocyanidins Restore the Metabolic Diurnal Rhythm of Subcutaneous White Adipose Tissue According to Time-Of-Day Consumption.

Consumption of grape seed proanthocyanidin extract (GSPE) has beneficial effects on the functionality of white adipose tissue (WAT). However, although WAT metabolism shows a clear diurnal rhythm, whether GSPE consumption could affect WAT rhythmicity in a time-dependent manner has not been studied. Ninety-six male Fischer rats were fed standard (STD, two groups) or cafeteria (CAF, four groups) diet for 9 weeks (n = 16 each group). From week 6 on, CAF diet animals were supplemented with vehicle or 25 mg GSPE/kg of body weight either at the beginning of the light/rest phase (ZT0) or at the beginning of the dark/active phase (ZT12). The two STD groups were also supplemented with vehicle at ZT0 or ZT12. In week 9, animals were sacrificed at 6 h intervals (n = 4) to analyze the diurnal rhythms of subcutaneous WAT metabolites by nuclear magnetic resonance spectrometry. A total of 45 metabolites were detected, 19 of which presented diurnal rhythms in the STD groups. Although most metabolites became arrhythmic under CAF diet, GSPE consumption at ZT12, but not at ZT0, restored the rhythmicity of 12 metabolites including compounds involved in alanine, aspartate, and glutamate metabolism. These results demonstrate that timed GSPE supplementation may restore, at least partially, the functional dynamics of WAT when it is consumed at the beginning of the active phase. This study opens an innovative strategy for time-dependent polyphenol treatment in obesity and metabolic diseases.

Structured Long-Chain Omega-3 Fatty Acids for Improvement of Cognitive Function during Aging.

Although the human lifespan has increased in the past century owing to advances in medicine and lifestyle, the human healthspan has not kept up the same pace, especially in brain aging. Consequently, the role of preventive health interventions has become a crucial strategy, in particular, the identification of nutritional compounds that could alleviate the deleterious effects of aging. Among nutrients to cope with aging in special cognitive decline, the long-chain omega-3 polyunsaturated fatty acids (ω-3 LCPUFAs) docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), have emerged as very promising ones. Due to their neuroinflammatory resolving effects, an increased status of DHA and EPA in the elderly has been linked to better cognitive function and a lower risk of dementia. However, the results from clinical studies do not show consistent evidence and intake recommendations for old adults are lacking. Recently, supplementation with structured forms of EPA and DHA, which can be derived natural forms or targeted structures, have proven enhanced bioavailability and powerful benefits. This review summarizes present and future perspectives of new structures of ω-3 LCPUFAs and the role of "omic" technologies combined with the use of high-throughput in vivo models to shed light on the relationships and underlying mechanisms between ω-3 LCPUFAs and healthy aging.

Regulation of p27 and Cdk2 Expression in Different Adipose Tissue Depots in Aging and Obesity.

Aging usually comes associated with increased visceral fat accumulation, reaching even an obesity state, and favoring its associated comorbidities. One of the processes involved in aging is cellular senescence, which is highly dependent on the activity of the regulators of the cell cycle. The aim of this study was to analyze the changes in the expression of p27 and cdk2 in different adipose tissue depots during aging, as well as their regulation by obesity in mice. Changes in the expression of p27 and CDK2 in visceral and subcutaneous white adipose tissue (WAT) biopsies were also analyzed in a human cohort of obesity and type 2 diabetes. p27, but not cdk2, exhibits a lower expression in subcutaneous than in visceral WAT in mice and humans. p27 is drastically downregulated by aging in subcutaneous WAT (scWAT), but not in gonadal WAT, of female mice. Obesity upregulates p27 and cdk2 expression in scWAT, but not in other fat depots of aged mice. In humans, a significant upregulation of p27 was observed in visceral WAT of subjects with obesity. Taken together, these results show a differential adipose depot-dependent regulation of p27 and cdk2 in aging and obesity, suggesting that p27 and cdk2 could contribute to the adipose-tissue depot's metabolic differences. Further studies are necessary to fully corroborate this hypothesis.