Development Of Metabolic Diseases Research Articles

EFFECTS OF ARTIFICIAL SWEETENERS ON HUMAN HEALTH

The health impacts of artificial sweeteners, which are commonly used as low-calorie sugar alternatives to treat diseases including diabetes and obesity, may be more complicated than previously thought, according to new research. Intriguingly, excessive intake has been linked to a higher risk of metabolic disorders, cardiovascular diseases, some types of cancer, weight gain, unfavourable pregnancy outcomes, and possible hazards for people with low seizure thresholds. Artificially sweetened beverages have been associated in studies, such as the Women's Health Initiative, with an increased risk of stroke, coronary heart disease, and death, regardless of known risk factors. ASs like saccharin have been connected to inflammatory bowel disorders, disruption of the gut microbiota, increased intestinal permeability, and dysbiosis, which can result in metabolic problems like impaired glucose tolerance, insulin resistance, and increased systemic inflammation. These concerns also extend to gut health. The development of metabolic diseases like type 2 diabetes mellitus is further facilitated by these disturbances, which lower the generation of short-chain fatty acids essential for insulin sensitivity. Given these possible health hazards, this review emphasizes the need for careful use, knowledgeable consumer choices, and strict regulatory monitoring. It also highlights the need for additional research to clarify long-term health impacts and create risk-reduction plans. Keywords: Artificial Sweeteners, Health Risks, Side Effects, Health

Biologic therapy for psoriasis is associated with the development of metabolic dysfunction-associated steatotic liver disease (MASLD). A study on the association of cardiometabolic conditions with psoriasis treatment.

Psoriasis requires a comprehensive assessment of concomitant diseases to make better therapeutic decisions. This study examined the differences in the onset and progression of associated cardiometabolic comorbidities in psoriasis patients based on their treatments. A retrospective longitudinal study was conducted on patients aged over 13 years with psoriasis seen at a Northern Mexican Hospital between 2012 and 2023. Patients were categorized into three groups according on the type of treatment received: topical, systemic, and biologic. A logistic regression analysis was performed to identify predictors of comorbidity development. 197 patients were included; 52.8% were women, with a mean (SD) age of 54.45 (16.91) years, divided into topical [n = 90 (45.7%)], systemic [n = 57 (29.1%)], and biologic [n = 50 (25.5%)] groups, metabolic dysfunction-associated steatotic liver disease (MASLD) was significantly more prevalent in the biologic group [22 (44%)], p < 0.001. The logistic regression showed that type 2 diabetes mellitus, biological treatments (OR = 5.798, p = 0.001), and body mass index (OR = 1.144, p = 0.002), predicted the development of MASLD with a Nagelkerke's R2 of 0.400. Psoriasis patients using biological therapies have a greater predisposition to MASLD. These patients should receive a comprehensive approach to identify metabolic conditions, and screening tests for MASLD are recommended.

Hindlimb Unloading Induces Apoptosis and Autophagy but Not Neurodegeneration in the Hippocampus of the Rats

Physical activity is well known to have a beneficial effect on whole body functions, whereas a sedentary lifestyle contributes to the development of metabolic and other diseases and can lead to cognitive decline and increased risk of dementia. The hippocampus mainly controls cognitive performance and the hippocampal neurodegeneration is directly correlated with dementia progression. Hindlimb unloading (HU) is a widely used method to simulate microgravity in rodents and can be used as a model of mobility restriction since one of the main factors of HU is muscle disuse. Additionally, rodents show impaired learning and memory after long-term HU. Here, we explored whether HU would affect the survival or death of the hippocampal cells. Our data demonstrated that after 3-day HU, both apoptosis and autophagy were activated in the hippocampus, as evidenced by the activation of caspase 3 and 9 and an increase in the number of Cathepsin D and LC3b double-positive cells correspondently. Our data indicated that HU has no deleterious effects leading to neurodegeneration for up to 14 days. Moreover, our results also showed that the activation of autophagy during short-term HU had a protective effect, as we did not observe any cell loss or damage.

Post-translational histone modifications associated with the development of metabolic dysfunction-associated fatty liver disease. Part 2. Histone methylation

Based on the analysis of literary sources of databa­ses Pubmed, MEDLINE, The Cochrane Library, Embase, the authors highlight the essential role of epigenetic modulations in the pathogenesis of metabolic dysfunction-associated fatty liver disease. They give general provisions regarding post-translational histone modifications, which are associated with the development of metabolic dysfunction-associated fatty liver disease, namely, the features of their methylation, post-translational modifications of methylation of lysine residues (sites H3K4, H3K27, H3K36, H3K79, H4K20, H3K23, H3K63 and H4K12), arginine residues (sites H2AR3, H4R3, H3R2, H3R8 and H3R26). Histone methy­lation and demethylation, mediating the expression of key genes involved in carbohydrate and lipid metabolism, determine both the occurrence and development of steatosis, inflammation and fibrosis of the liver in patients with metabolic dysfunction-­associated fatty liver disease. Methylated markers H3K9, H3K27, H4K20 of histones are associated with packed heterochromatin and repression of gene transcription, while methylated markers H3K4, H3K36, H3K79 of histones are associated with activation of gene transcription. Methylation of lysine or arginine residues of histones is carried out by methyltransferases that use S-adenosylmethionine as a donor molecule. The methylated site of an arginine residue can be represented by a monomethylated, asymmetrically demethylated, or symmetrically demethylated marker, whereas demethylation of a lysine marker is mediated by demethylases. The authors provide data that in metabolic dysfunction-associated fatty liver disease, the main sites in which aberrant methylation is observed are H3K4, H3K9, H3K27, H4R3, H3R8, and H2AR3. Several genes of histone methyltransferases and histone demethylases have been identified, which are differentially expressed in patients with metabolic dysfunction-associated fatty liver disease and healthy people. The authors emphasize that the enzymes involved in the histone methylation and demethylation are targets of future drugs, which will certainly improve the effectiveness of drug therapy in patients with metabolic dysfunction-associated fatty liver disease.

NORAD exacerbates metabolic dysfunction-associated steatotic liver disease development via the miR-511-3p/Rock2 axis and inhibits ubiquitin-mediated degradation of ROCK2.

Abnormal expression of long noncoding RNAs is strongly linked to metabolic dysfunction-associated steatotic liver disease (MASLD). However, the precise molecular mechanisms remain unclear. This study explores the roles of noncoding RNA activated by DNA damage (NORAD)/miR-511-3p/Rho-associated protein kinase 2 (Rock2) axis and the NORAD/ROCK2 interaction in the development of MASLD. In vitro and in vivo models of MASLD were created using high-fat diet-fed mice and free fatty acid (FFA)-treated hepatocytes. To examine the relationships between NORAD, miR-511-3p, and ROCK2, we employed bioinformatics, luciferase assays, RNA immunoprecipitation, and biotinylated NORAD pull-down assays. MASLD progression was assessed based on food intake, energy expenditure, insulin resistance, hepatic steatosis, inflammation, white fat growth, and liver fibrosis. NORAD and ROCK2 were upregulated, while miR-511-3p was downregulated in MASLD liver tissues and FFA-treated hepatocytes. Mechanistically, NORAD competitively interacted with miR-511-3p to modulate Rock2 mRNA expression, and directly stabilized ROCK2 protein by abrogating its ubiquitination degradation. Functionally, liver-specific knockdown of NORAD or overexpression of miR-511-3p significantly slowed MASLD progression. Overexpression of NORAD or ROCK2 partially reversed miR-511-3p-induced inhibition of MASLD. Additionally, ROCK2 knockdown attenuated NORAD-induced worsening of MASLD. Moreover, overexpressing NORAD or ROCK2 or interfering miR-511-3p influenced resmetirom treatment to suppress MASLD development. Finally, metabolic changes in liver driven by the NORAD/miR-511-3p/Rock2 axis and NORAD/ROCK2 interaction also influenced white adipose growth, pancreatic β-cell dedifferentiation, and liver fibrosis. The NORAD/miR-511-3p/Rock2 axis and the NORAD/ROCK2 interaction play critical roles in MASLD progression, identifying potential therapeutic targets for its treatment.

Association between volatile organic compounds and circadian syndrome among pre- and postmenopausal women: A population-based study.

Air pollution is closely associated with the development of multiple metabolic diseases. Circadian syndrome (CircS), as an extended concept of metabolic syndrome (MetS), has been proven to be a better predictor of metabolic diseases than MetS. However, the relationship between volatile organic compounds (VOCs) and CircS in pre- and postmenopausal remains unclear. This study used data from the National Health and Nutrition Examination Survey (NHANES) 2011-2020, including 520 premenopausal women and 531 postmenopausal women. Generalized linear model (GLM), restricted cubic splines (RCS) model, subgroup analyses, and weighted quantile sum (WQS) model was used to assess the relationship between VOCs and CircS. In addition, sensitivity analyses were performed to evaluate the robustness of the results. Our findings showed that seven VOC metabolites were positively associated with the risk of CircS in postmenopausal women. In premenopausal women, only two VOC metabolites were positively associated with the risk of CircS. The WQS analysis further confirmed that VOC mixtures selected by least absolute shrinkage and selection operator (LASSO) were significantly associated with an increased risk of CircS in postmenopausal women, with HPMMA identified as the primary contributor to the combined effect. This association was not evident in premenopausal women. Meanwhile, in postmenopausal women, individual urinary VOC metabolites and VOC mixtures were observed to be positively associated with elevated glucose and short sleep. Our results highlighted that VOCs exposure was strongly associated with the occurrence of CircS in postmenopausal women. Further research is needed to confirm this conclusion.

Targeting GSK-3β for adipose dysfunction and cardiovascular complications of metabolic disease: Anentangled WNT/β-catenin question.

Individuals with metabolic syndrome have a high risk of developing cardiovascular disorders that is closely tied to visceral adipose tissue dysfunction, as well as an altered interaction between adipose tissue and the cardiovascular system. In metabolic syndrome, adipose tissue dysfunction is associated with increased hypertrophy, reduced vascularization, and hypoxia of adipocytes, leading to a pro-oxidative and pro-inflammatory environment. Among the pathways regulating adipose tissue homeostasis is the wingless-type mammary tumor virus integration site family (Wnt) signaling pathway, with both its canonical and non-canonical arms. Various modulators of the Wnt signaling have been identified to contribute to the development of metabolic diseases and their cardiovascular complications, with a particularly significant role played by Glycogen Synthase Kinase-3β (GSK-3β). GSK-3β levels and activities have various and often contrasting roles in obesity and related metabolic disorders, as well as their cardiovascular sequelae. Here, we explore the possibility that altered Wnt signaling and GSK-3β activities could serve as a connection between adipose tissue dysfunction and the development of cardiovascular disease in individuals with metabolic syndrome. We attempt to define a context-specific approach for intervention, which could possibly serve as a novel disease modifying therapy for the mitigation of such complications.

Modulating intestinal viruses: A potential avenue for improving metabolic diseases with unresolved challenges.

The gut microbiome affects the occurrence and development of metabolic diseases, with a significant amount of research focused on intestinal bacteria. As an important part of the gut microbiome, gut viruses were studied recently, particularly through fecal virome transplantation (FVT), revealing manipulating the gut virus could reverse overweight and glucose intolerance in mice. And human cohort studies found gut virome changed significantly in patients with metabolic disease. By summarizing those studies, we compared the research and analytical methods, as well as the similarities and differences in their results, and analyzed the reasons for these discrepancies. FVT provided potential value to improve metabolic diseases, but the mechanisms involved and the effect of FVT on humans should be investigated further. The potential methods of regulating intestinal virome composition and the possible mechanisms of intestinal virome changes affecting metabolic diseases were also discussed.

Association of neutrophil-to-lymphocyte ratio and risk of all-cause and cardiovascular mortality in adults with metabolic dysfunction-associated steatotic liver disease: a population-based cohort study.

Inflammation is key to metabolic dysfunction-associated steatotic liver disease (MASLD) development. Nevertheless, the correlation between the inflammatory marker, neutrophil-to-lymphocyte ratio (NLR), and the MASLD prognosis remains unclear. We aim to determine the link between NLR and mortality risk in MASLD. The MASLD adult participants from the 1999-2018 National Health and Nutrition Examination Survey (NHANES) database were evaluated. Utilizing restricted cubic spline (RCS) analyses, as well as Cox proportional hazards (PH) models, the associations between NLR and all-cause mortality (ACM) and cardiovascular mortality (CVM) were analyzed in MASLD. Subgroup analyses and interaction tests were conducted to validate these associations. Moreover, we used sensitivity analyses to ascertain the robustness of the results. Through 115 months of median follow-up, 2,307 of the 16,859 participants with MASLD died, including 650 deaths from cardiovascular causes. RCS analyses showed positive linear associations between NLR and both ACM and CVM. In the multivariable-adjusted Cox PH model, a one-unit elevation in NLR was related to a hazard ratio (HR) of 1.16 (95% confidence interval [CI]: 1.12-1.21) for ACM and 1.21 (95% CI: 1.15-1.27) for CVM. Participants were classified into higher (≥ 2.88) and lower (< 2.88) NLR groups employing the maximally selected rank statistics. The higher NLR group had a significantly elevated ACM (HR 1.38, 95% CI: 1.23-1.55) and CVM (HR 1.64, 95% CI: 1.32-2.03) risk compared to the lower NLR group. The associations were consistent in subgroup analyses based on age, gender, BMI, hypertension, and diabetes, with no significant interaction between NLR and these characteristics. Sensitivity analyses affirmed the main outcome's robustness. A raised NLR independently predicts escalated ACM and CVM in MASLD.

Pathobiochemistry of Aging and Neurodegeneration: Deregulation of NAD+ Metabolism in Brain Cells.

NAD+ plays a pivotal role in energy metabolism and adaptation to external stimuli and stressful conditions. A significant reduction in intracellular NAD+ levels is associated with aging and contributes to the development of chronic cardiovascular, neurodegenerative, and metabolic diseases. It is of particular importance to maintain optimal levels of NAD+ in cells with high energy consumption, particularly in the brain. Maintaining the tissue level of NAD+ with pharmacological tools has the potential to slow down the aging process, to prevent the development of age-related diseases. This review covers key aspects of NAD+ metabolism in terms of brain metabolic plasticity, including NAD+ biosynthesis and degradation in different types of brain cells, as well as its contribution to the development of neurodegeneration and aging, and highlights up-to-date approaches to modulate NAD+ levels in brain cells.

Endothelial Angpt2 Promotes Adipocyte Progenitor Cells Maturation to Increase Visceral Adipose Tissue Accumulation.

Visceral adipose tissue (VAT) accumulation is essential for the occurrence and development of obesity and related metabolic diseases. Currently, the specific mechanism of VAT accumulation is still unclear. We searched the Gene Expression Omnibus database to obtain single-cell RNA sequencing (scRNAseq) data for VAT in patients with a normal body mass index (BMI), obesity, or morbid obesity. By using PCR, WB, immunofluorescence staining, and flow cytometry analysis, we validated the interactions between macrophages, endothelial cells (ECs), and adipocyte progenitor cells (APCs), as well as the underlying mechanism, in VAT. Finally, we tested the findings in obese mice using recombinant proteins and adeno-associated virus infection. One study with human scRNAseq data was included. This study collected 13-VAT from 5 individuals with obesity and diabetes, 9 individuals with obesity, and 1 individual with a normal BMI. The proportion of inflammatory macrophages is substantially increased in obese and diabetic patients. ECs have the most active interactions with other cells. Notably, the activation of JAK1/STAT3 is one of the reasons for the increase in inflammatory endothelial cells and can promote the secretion of angiopoietin-2 (Angpt2) and induce APCs to transition from mesothelin (MSLN) to complement factor D (CFD) expression via integrin-α5β1 signalling. This phenotypic transition promotes APC differentiation into mature adipocytes and accelerates VAT accumulation. These observations were further validated in an in vitro model and an in vivo study using Angpt2 recombinant proteins and blocking the expression of Angpt2 by adeno-associated virus infection. ECs are essential for promoting VAT accumulation by facilitating APC differentiation from MSLN to CFD phenotype. This process is driven by Angpt2 from ECs upon JAK1/STAT3 signalling activation under metabolic stress.

Adipose tissue insulin resistance in children and adolescents: linking glucose and free fatty acid metabolism to hepatic injury markers.

Obesity is one of the leading causes of the development of insulin resistance, diabetes, and metabolic dysfunction-associated steatotic liver disease (MASLD) in children. With the progression of insulin resistance, both glucose and free fatty acid (FFA) plasma levels are elevated, leading to cardiometabolic complications such as impaired glucose tolerance (IGT), type 2 diabetes, and liver fat accumulation. In this study, oral minimal models were used to estimate insulin sensitivity indexes (SI and SIFFA) in 375 adolescents with obesity. Differences between normal glucose tolerance (NGT) and IGT were assessed by using Mann-Whitney U test, while the relationship between insulin sensitivities and plasma alanine transaminase (ALT) was assessed using Spearman correlation and linear regression model of the log-transformed variables. Also, 48 youths repeated the oral glucose tolerance test and the measurement of liver function test after ∼1.3 yr of follow-up. SI was statistically different between NGT and IGT (P < 10-6) and correlated with each other (ρ = 0.7, P < 10-6). Lipolysis was completely suppressed after 30 min in NGT, compared with 120 min in IGT. SI and SIFFA were both statistically correlated with ALT (ρ = -0.19, P < 10-3). Also, the percentages of variation of SIFFA and ALT between the first and second visits correlated significantly (ρ = -0.47, P = 0.002). FFA minimal model can be used to estimate adipose tissue lipolysis in youths with obesity. The relationship of SI and SIFFA with ALT, along with the progression of the impairment of adipose tissue insulin sensitivity, shows that systemic insulin resistance underlies the relationship of glucose and FFA metabolism with hepatic damage.NEW & NOTEWORTHY In this study, we applied glucose, Cpeptide, and FFA minimal models to assess insulin sensitivities, insulin secretion, and lipolytic flux in NGT and IGT in adolescents with obesity. The results show that glucose and adipose tissue insulin sensitivities are strongly correlated with each other and with ALT plasma level. The longitudinal results show that changes in FFA insulin sensitivity are inversely associated with changes of beta cell secretion and with biomarkers of metabolic dysfunction-associated steatohepatitis.

Silymarin-Enriched Extract from Milk Thistle Activates Thermogenesis in a Preclinical Model of High-Fat-Diet-Induced Obesity to Relieve Systemic Meta-Inflammation.

Obesity and aging are associated with the progressive loss of brown adipose tissue (BAT), an increase in visceral white adipose tissue (vWAT), and a reduction in subcutaneous white adipose tissue (sWAT). The progressive expansion of visceral obesity promotes a low grade of systemic chronic inflammation (meta-inflammation), contributing to the onset of comorbidities such as type 2 diabetes mellitus (T2DM), metabolic syndrome, and even cancer. Thus, preserving the thermogenic activity of adipose tissue and improving the metabolic flexibility of sWAT could be an effective strategy to prevent the development of metabolic chronic diseases and promote healthy aging. Precision nutrition has emerged as a complementary approach to control the metabolic alterations associated with unhealthy obesity and aging. In a previous work, we described that a silymarin-enriched extract from milk thistle (Mthistle) increased markers of browning and thermogenesis in vitro in human differentiated adipocytes (SGBS). Therefore, this study aims to evaluate the potential of Mthistle to activate thermogenesis in a preclinical model of high-fat diet (HFD)-induced obesity (DIO). Our results demonstrate that Mthistle increases systemic energy expenditure (EE), preserves body temperature after cold exposure, improves insulin resistance, and reduces inflammatory markers in WAT. Based on these results, silymarin-enriched extract from Mthistle may be proposed as a nutraceutical for the management of metabolic chronic diseases and/or accelerated aging.

Automated MRI quantification of pediatric abdominal adipose tissue using convolutional neural networks and novel total intensity maps

ObjectiveChildhood obesity is a significant global health concern. Visceral adipose tissue (VAT) is more closely linked to the development of metabolic and cardiovascular diseases than abdominal subcutaneous adipose tissue (ASAT). This study aimed to develop a straightforward and automated method to quantify both ASAT and VAT in children from MRI. MethodsDixon-based 3 T-MRI scans were conducted on Mexican boys aged 7–9 years. Novel Total Intensity Maps were generated from these scans for input into simple 2D Convolutional Neural Networks (CNNs) for automatic prediction/quantification of ASAT and VAT. The results were compared with the commercial semi-automated quantification and validated method provided by AMRA® Researcher which is the gold standard. ResultsThe CNN-based method produced ASAT and VAT quantifications comparable to those obtained by AMRA® Researcher (ASAT, p = 0.1765; VAT, p = 0.7757), with a high correlation between the two methods for ASAT (R2 = 0.98, p < 10−14) and VAT (R2 = 0.95, p < 10−11). The reproducibility coefficients (RPC) were 0.32 L for ASAT and 0.17 L for VAT with our novel methodology. ConclusionThis study presents a simple automated method for quantifying ASAT and VAT in children from MRI data using 2D-CNN analysis of novel inputs, Total Intensity Maps. The new method produced measurements comparable to those obtained by AMRA® Researcher on the same dataset. SignificanceThe proposed automatic and straightforward quantification method, with minimal computational resource requirements, may serve as an accessible tool for researchers and clinicians in the diagnosis, follow-up, and prevention of childhood obesity.

Insights into risk factors of the Metabolic Dysfunction-Associated Steatotic Liver Disease development among patients with schizophrenia

Insights into risk factors of the Metabolic Dysfunction-Associated Steatotic Liver Disease development among patients with schizophrenia

Therapeutic Effects of Taurine and Histidine Supplementation in Retinal Diseases.

Amino acids are basic building blocks of structural proteins and enzymes. They also act as signaling molecules and as fuel. They are characterized as essential if sufficient quantities must be supplied exogenously or as non-essential if they can be endogenously synthesized. Appropriate intake of amino acids not only prevents the development of metabolic diseases but also can reduce the progression of some disease states. Amino acids are strongly associated with retinal metabolism in physiology and pathology. Nonetheless, there is a lack of robust clinical studies supporting the benefits of amino acid supplementation in retinopathy. In this review, we summarize preclinical evidence concerning the potential of supplementing the amino acids taurine and histidine to provide protection against diabetic retinopathy, glaucoma, and age-related macular degeneration. We suggest further directions for studying amino acid-based therapeutic interventions for eye diseases.

Sex differences in skeletal muscle metabolism in exercise and type 2 diabetes mellitus.

This Review focuses on currently available literature describing sex differences in skeletal muscle metabolism in humans, as well as highlighting current research gaps within the field. These discussions serve as a call for action to address the current lack of sufficient sex-balanced studies in skeletal muscle research, and the resulting limitations in understanding sex-specific physiological and pathophysiological responses. Although the participation of women in studies has increased, parity between the sexes remains elusive, affecting the validity of conclusions drawn from studies with limited numbers of participants. Changes in skeletal muscle metabolism contribute to the development of metabolic disease (such as type 2 diabetes mellitus), and maintenance of skeletal muscle mass is a key component for health and the ability to maintain an independent life during ageing. Exercise is an important factor in maintaining skeletal muscle health and insulin sensitivity, and offers promise for both prevention and treatment of metabolic disease. With the increased realization of the promise of precision medicine comes the need to increase patient stratification and improve the understanding of responses in different populations. In this context, a better understanding of sex-dependent differences in skeletal muscle metabolism is essential.

Natriuretic peptide levels and predicting risk of developing new diabetes mellitus and metabolic syndrome.

Define the relationship between N-terminal atrial natriuretic peptide (NT-ANP) levels and incident metabolic syndrome and type 2 diabetes mellitus ('metabolic disease') in healthy adults and develop a risk prediction score. Retrospective cohort study of Olmsted County Heart Function Study participants, a random sampling of county residents aged 45 years and older (n = 2042). Clinical data were collected during enrolment between 1997 and 2000 and upon follow-up 4 years later. Outcomes were followed for 8 years. We studied 715 subjects without metabolic disease at enrolment who completed follow-up, assessing incident metabolic disease as the primary outcome. Youden's index was used to identify optimal cut-points and develop the risk score. Upon multivariate analysis adjusting for age gender, HDL and triglycerides, higher baseline serum NT-ANP levels were associated with a lower risk of metabolic disease (OR: 0.65, CI 0.49-0.85, p = 0.002). Higher baseline serum insulin and aldosterone levels were associated with higher risk of incident metabolic disease (OR: 2.04, CI 1.57-2.65, p < 0.001; OR: 1.43, CI 1.14-1.81, p = 0.002, respectively). Baseline serum NT-ANP < 3337 pg/mL was 96.6% sensitive for future development of metabolic disease. A weighted score including all three biomarkers was 78.6% sensitive and 77.3% specific. In healthy adults aged 45 years or older, higher baseline NT-ANP levels are associated with a lower four-year risk of developing metabolic disease. Serum NT-ANP levels are a sensitive biomarker of future risk of metabolic disease and have screening utility when combined with insulin and aldosterone levels into a composite score.

Contribution of glucose and glutamine to hypoxia-induced lipid synthesis decreases, while contribution of acetate increases, during 3T3-L1 differentiation

The molecular mechanisms linking obstructive sleep apnea syndrome (OSA) to obesity and the development of metabolic diseases are still poorly understood. The role of hypoxia (a characteristic feature of OSA) in excessive fat accumulation has been proposed. The present study investigated the possible effects of hypoxia (4% oxygen) on de novo lipogenesis by tracking the major carbon sources in differentiating 3T3-L1 adipocytes. Gas-permeable cultuware was employed to cultivate 3T3-L1 adipocytes in hypoxia (4%) for 7 or 14 days of differentiation. We investigated the contribution of glutamine, glucose or acetate using 13C or 14C labelled carbons to the newly synthesized lipid pool, changes in intracellular lipid content after inhibiting citrate- or acetate-dependent pathways and gene expression of involved key enzymes. The results demonstrate that, in differentiating adipocytes, hypoxia decreased the synthesis of lipids from glucose (44.1 ± 8.8 to 27.5 ± 3.0 pmol/mg of protein, p < 0.01) and partially decreased the contribution of glutamine metabolized through the reverse tricarboxylic acid cycle (4.6% ± 0.2–4.2% ± 0.1%, p < 0.01). Conversely, the contribution of acetate, a citrate- and mitochondria-independent source of carbons, increased upon hypoxia (356.5 ± 71.4 to 649.8 ± 117.5 pmol/mg of protein, p < 0.01). Further, inhibiting the citrate- or acetate-dependent pathways decreased the intracellular lipid content by 58% and 73%, respectively (p < 0.01) showing the importance of de novo lipogenesis in hypoxia-exposed adipocytes. Altogether, hypoxia modified the utilization of carbon sources, leading to alterations in de novo lipogenesis in differentiating adipocytes and increased intracellular lipid content.

Adipocyte-Targeted Nanotechnology and Cell-Based Therapy for Obesity Treatment.

Obesity is a critical risk factor for the development of metabolic diseases and is often associated with dysfunctional adipocytes. Prevalent treatments such as lifestyle intervention, pharmacotherapy, and bariatric surgery are often accompanied by adverse side effects and poor patient compliance. Nanotechnology and cell-based therapy offer innovative approaches for targeted obesity treatments, as they can directly target adipocytes, regulate lipid metabolism, and minimize off-target effects. Here, we provide an overview of the intricate relationship between adipocytes and obesity, highlighting the potential of nanotechnology and cell-based therapy in obesity treatment. Additionally, we discuss the advancements of adipose-derived mesenchymal stem cells (ADMSCs) in obesity progression, including the latest challenges and considerations for developing adipose-targeted treatments for obesity. The objective is to provide a perspective on the design and development of nanotechnology and cell-based therapy for treating obesity and related comorbidities.