Epidemiological evidence suggests that there is a direct relationship between the degree of obesity and acute pancreatitis severity. Intake of different fatty acids leads to different types of hyperlipidemias. Adipose degradation by pancreatic lipase generates different free fatty acids, which can exacerbate pancreatitis. Saturated fatty acids (SFAs) play an inflammatory role in human metabolic syndrome and obesity, whereas unsaturated fatty acids (UFAs) are "good fats" that are thought to enhance overall health status. However, it appears that serum UFAs correlate with severe acute pancreatitis. Additionally, the "obesity paradox" suggests that UFAs potentially minimize direct harm to the organ. This review provides an in-depth overview of the role of SFAs and UFAs in acute pancreatitis of hyperlipidemia and discusses potential prevention targets for severe acute pancreatitis.

In obesity, adipose tissue (AT) expansion is accompanied by chronic inflammation. Altered lipid composition in the visceral or gonadal white AT (GWAT) directly drive AT macrophage accumulation and activation to a proinflammatory phenotype. Sex steroid hormones modulate visceral versus subcutaneous lipid accumulation that correlates with metabolic syndrome, especially in men and postmenopausal women who are more prone to abdominal obesity. Prior studies demonstrated sex differences in GWAT lipid species in HFD-fed mice, but the role of sex hormones is still unclear. We hypothesized that sex hormone alterations with gonadectomy (GX) would further impact lipid composition in the obese GWAT. Untargeted lipidomics of obese GWAT identified sex differences in phospholipids, sphingolipids, sterols, fatty acyls, saccharolipids and prenol lipids. Males had significantly more precursor fatty acids (palmitic, oleic, linoleic, and arachidonic acid) than females and GX mice. Targeted lipidomics for fatty acids and oxylipins in the HFD-fed male and female GWAT stromal vascular fraction identified higher omega-6 to omega-3 free fatty acid profile in males and differences in PUFAs-derived prostaglandins, thromboxanes, and leukotrienes. Both obese male and female GWAT stromal vascular fraction showed increased levels of arachidonic acid-derived oxylipins compared to their lean counterparts. Bulk RNA-seq of sorted GWAT AT macrophages highlighted sex and diet differences in PUFA and oxylipin metabolism genes. These findings of sexual dimorphism in both stored lipid species and PUFA-derived mediators with diet and GX emphasize sex differences in lipid metabolism pathways that drive inflammation responses and metabolic disease risk in obesity.

Recent studies found that palmitic acid (PA), the most abundant fatty acid in human body, was increased in uveitis patients. However, its exact effect on uveitis has not been clarified. In this study, experimental autoimmune uveitis (EAU), an animal model of human uveitis, was successfully induced with interphotoreceptor retinoid-binding protein (IRBP) 651-670 and pertussis toxin. The immunized mice were treated with daily intragastric PA or vehicle from day 1-14. The results showed that PA could aggravate EAU activities and increase the proportion of T helper (Th) 17 cells as well as mRNA expression level of Il17a. There were no significant changes in Th1/Treg cell responses between these two groups. In vitro experiments showed that PA treatment could promote IRBP-specific Th17 cell response in association with increased proportion of Th17 cells as well as up-regulated expression of IL-17A. Proteomics showed an increased expression of stimulator of interferon genes protein (STING) in PA-treated mice as compared to vehicle-treated mice. H-151, a potent antagonist of STING, attenuated the activities of EAU and Th17 cell responses induced by PA. Moreover, NF-κB/IL-6 signaling pathway was found to be downregulated after H-151 treatment. Collectively, PA could exacerbate EAU severity possibly through the activation of Th17 cells mediated by up-regulating STING.

Cancer is a disease influenced by both genetic and environmental factors, with dietary lipids being a significant contributing factor. This review summarizes the role of polyunsaturated fatty acids (PUFAs) in the mechanism of tumor occurrence and development, and elucidate the role of PUFAs in tumor treatment.

PUFAs exert their impact on cancer through altering lipid composition in cell membranes, interacting with cell membrane lipid receptors, directly modulating gene expression in the cell nucleus, and participating in the metabolism of lipid mediators. Most omega-3 PUFAs are believed to inhibit cell proliferation, promote cancer cell death, suppress cancer metastasis, alter energy metabolism, inhibit tumor microenvironment inflammation, and regulate immune responses involving macrophages, T cells, NK cells, and others. However, certain omega-6 PUFAs exhibit weaker anti-tumor effects and may even promote tumor development, such as by fostering inflammatory tumor microenvironment and enhancing tumor cell proliferation. PUFAs play important roles in hallmarks of cancer including tumor cell proliferation, cell death, migration and invasion, energy metabolism remodeling, epigenetics, and immunity. These findings provide insights into the mechanisms of cancer development and offers options for dietary management of cancer.

This study investigated the effects of dietary Cannabis sativa residues (CR) on broiler growth and meat characteristics. A total of 256 one-day-old male Ross-308 broilers were randomly assigned to four treatments: a basal diet (control) and diets containing 0.5%, 1%, and 2% CR. CR supplementation had no effect on growth performance, survival rate, or European production index but reduced average daily feed intake (p < 0.01). No significant differences were found in meat pH, color, drip loss, thawing loss, cooking loss, or shear force (p > 0.05). However, the ΔE values (0.5% CR: 3.97, 1.0% CR: 3.71, 2.0% CR: 4.95) indicated perceptible color differences compared to the control. CR significantly reduced C12:0, C20:1n9, and C22:1n9 fatty acids (p < 0.05) while increasing free amino acids, including aspartic acid, serine, proline, methionine, and phenylalanine (p < 0.05). It also increased moisture content and decreased fat content, especially at 2% CR (p < 0.05). In conclusion, CR supplementation improves the flavor and nutritional value of broiler meat and is a potential alternative to conventional feed additives.

Triglyceride glucose (TyG) index and atherogenic index of plasma (AIP) are indicators of insulin resistance. However, inadequate evidence indicates that the TyG index, AIP, and chronic pain are linked.

Data from the National Health and Nutrition Examination Survey (NHANES) between 1999 and 2004 were used. Directed acyclic graphs were used to identify 11 potential confounders. The TyG index and AIP were treated as continuous variables in the multivariate logistic regression models to assess their association with chronic pain. Furthermore, the nonlinear relationships between these indices and outcomes were investigated using restricted cubic spline plots. Subsequently, subgroup analyses were conducted for the sensitive populations. Receiver operating characteristic curves were used to compare the relationships between indices and outcomes. Ultimately, two sensitivity analyses were performed.

This study identified nonlinear associations between the TyG index, AIP, and chronic pain in 16,996,513 Americans. The odds ratio and 95% confidence interval for the TyG index (per 1 standard deviation increase) was 1.17 (1.02, 1.33), and for AIP (per 1 standard deviation increase) was 1.19 (1.07, 1.34). According to the subgroup analyses, the relationships between exposure and outcome were more pronounced in the non-diabetic population. The TyG index and AIP performed similarly in assessing chronic pain in ROC curves. Additionally, the results of the two sensitivity analyses matched the conclusions of the main study.

Nonlinear correlations between the TyG index, AIP, and chronic pain were identified among adults in the United States. This demonstrated that the TyG index and AIP displayed similar effectiveness in predicting the risk of chronic pain.

Background: Vegan/vegetarian (VEG) restaurants and VEG options in omnivore (OMNI) restaurants may serve unhealthful plant-based food that may be more harmful than a typical American diet. Methods: A sample of 561 restaurants with online menus were analyzed over a 3-year period. Each plant-based menu entrée was counted, up to a maximum of ten entrées per restaurant, meaning that a restaurant customer could select from ten or more healthful plant-based choices. Entrées containing refined grains (e.g., white rice and refined flour), saturated fat (e.g., palm oil and coconut oil), or deep-fried foods were counted as zero. Results: We evaluated 278 VEG and 283 OMNI restaurants. A full menu (10 or more plant-based entrées) was available in 59% of the VEG, but only 16% of the OMNI (p < 0.0001). Zero healthful options occurred in 27% of OMNI, but only 14% of VEG (p = 0.0002). The mean healthy entrée count for all restaurants was 3.2, meaning that, on average, there were only about three healthful plant-based choices of entrées on the menu, significantly more in VEG (4.0 vs. 2.4 p < 0.0001). The most common entrée reduction was for refined grains (e.g., white flour in veggie-burger buns or white rice in Asian entrées, n = 1408), followed by fried items (n = 768) and saturated fat (n = 318). VEG restaurants had a significantly higher frequency of adequate VEG options (≥7 options, 24% vs. 13%, p = 0.0005). Conclusions: Restaurants listed as VEG have a slightly higher number of healthful entrées than OMNI restaurants, which offer more limited vegan/vegetarian options. Given the published relationship between unhealthful dietary patterns, chronic illness, and mortality, we propose that detailed nutrition facts be publicly available for every restaurant.

This study investigated the chemopreventive mechanisms of fish oil (FO) at different doses and administration routes in skin carcinogenesis induced by 7,12-dimethylbenz[a]anthracene (DMBA) and croton oil (CO) in Swiss albino mice. Seventy mice were divided into 10 groups, including controls and those receiving FO either orally or topically, with or without the carcinogenesis protocol. Warts were morphologically analyzed. Anatomopathological analysis, qRT-PCR of nuclear factor kappa B (NF-қB) subunits' gene expression, and evaluation of oxidative parameters were conducted. Anatomopathological analysis revealed a presence of invasive squamous cell carcinoma (SCC) in DMBA group. Both oral (500 mg/kg/day) and topical FO treatment showed no signs of cancer, while oral administration at 50 mg/kg/day had no therapeutic effect, and 250 mg/kg/day resulted in low-grade malignancy. Both oral (250 and 500 mg/kg/day) and topical FO significantly reduced NF-кB1 gene expression, alleviated oxidative stress markers, and restored antioxidant enzyme activities compared to the DMBA group. FO shows dose-dependent chemopreventive effects, with oral administration potentially as effective as topical application when using an appropriate dosage. The development of SCC is linked to the stress status and the upregulation of the canonical NF-κB pathway, while FO's chemoprotective effects likely result from its downregulation.

The liver plays a central role in fat storage, but little is known about physiological fat accumulation during early development. Here we investigated a transient surge in hepatic lipid droplets observed in newborn mice immediately after birth. We developed a novel model to quantify liver fat content without tissue processing. Using high-resolution microscopy assessed the spatial distribution of lipid droplets within hepatocytes. Lugol's iodine staining determined the timing weaning period, and milk deprivation experiments investigated the relationship between milk intake and fat accumulation. Lipidomic analysis revealed changes in the metabolic profile of the developing liver. Finally, we investigated the role of Toll-like receptor 4 (TLR4) signaling in fat storage using knockout mice and cell-specific deletion strategies. Newborn mice displayed a dramatic accumulation of hepatic lipid droplets within the first 12 h after birth, persisting for the initial two weeks of life. This pattern coincided with exclusive milk feeding and completely abated by the third week, aligning with weaning. Importantly, the observed fat accumulation shared characteristics with established models of pathological steatosis, suggesting potential biological relevance. Lipid droplets were primarily localized within the cytoplasm of hepatocytes. Milk deprivation experiments demonstrated that milk intake is the primary driver of this transient fat accumulation. Lipidomic analysis revealed significant changes in the metabolic profile of newborn livers compared to adults. Interestingly, several highly abundant lipids in newborns were identified as putative ligands for TLR4. Subsequent studies using TLR4-deficient mice and cell-specific deletion revealed that TLR4 signaling, particularly within hepatocytes, plays a critical role in driving fat storage within the newborn liver. Additionally, a potential collaboration between metabolic and immune systems was suggested by the observed effects of myeloid cell-specific TLR4 ablation. This study demonstrates a unique phenomenon of transient hepatic fat accumulation in newborn mice driven by milk intake and potentially regulated by TLR4 signaling, particularly within hepatocytes.

Although lipid-derived acetyl-coenzyme A (CoA) is a major carbon source for histone acetylation, the contribution of fatty acid β-oxidation (FAO) to this process remains poorly characterized. To investigate this, we generated mitochondrial acetyl-CoA acetyltransferase 1 (ACAT1, distal FAO enzyme) knockout macrophages. 13C-carbon tracing confirmed reduced FA-derived carbon incorporation into histone H3, and RNA sequencing identified diminished interferon-stimulated gene expression in the absence of ACAT1. Chromatin accessibility at the Stat1 locus was diminished in ACAT1-/- cells. Chromatin immunoprecipitation analysis demonstrated reduced acetyl-H3 binding to Stat1 promoter/enhancer regions, and increasing histone acetylation rescued Stat1 expression. Interferon-β release was blunted in ACAT1-/- and recovered by ACAT1 reconstitution. Furthermore, ACAT1-dependent histone acetylation required an intact acetylcarnitine shuttle. Last, obese subjects' monocytes exhibited increased ACAT1 and histone acetylation levels. Thus, our study identifies an intriguing link between FAO-mediated epigenetic control of type I interferon signaling and uncovers a potential mechanistic nexus between obesity and type I interferon signaling.

Growing evidence suggests that hyperglycemia-related abnormalities in Schwann cells play a pivotal role in the development and progression of diabetic peripheral neuropathy (DPN). Several immortalized Schwann cell lines have been established in our laboratory and utilized for the study of DPN; IMS32 from normal ICR mice, 1970C3 from normal C57BL/6 mice, IWARS1 and IKARS1 from wild-type and aldose reductase-deficient C57BL/6 mice, and IFRS1 from normal Fischer 344 rats. These cell lines retain biological features of Schwann cells and display high proliferative activities that enable us to perform molecular and biochemical analyses. In addition, these cells have exhibited metabolic alterations under exposure to diabetes-associated conditions, such as hyperglycemia, dyslipidemia, glycative and oxidative stress load. Herein, recent studies with these cell lines regarding the pathogenic factors of DPN (augmentation of the polyol and other collateral glycolysis pathways, glycative and oxidative stress-induced cell injury, autophagic and proteostatic disturbances, etc.) and therapeutic strategies targeting these factors are introduced.

Metabolic alterations are related to tumorigenesis and other age-related diseases that are accelerated by "Westernized" diets. In fact, hypercaloric nutrition is associated with an increased incidence of cancers and faster aging. Conversely, lifespan-extending strategies, such as caloric restriction, impose beneficial effects on both processes. Here, we investigated the metabolic consequences of hypercaloric-induced aging on tumor growth in female mice. Our findings indicate that a high-fat high-sucrose diet increases tumor growth mainly due to the boosted oxidation of glucose and fatty acids. Consequently, through an increased expression of lactate, IGFBP3, and PTHLH, tumors modulate liver and white adipose tissue metabolism. In the liver, the induced tumor increases fibrosis and accelerates the senescence process, despite the lower systemic pro-inflammatory state. Importantly, the induced tumor induces the wasting and browning of white adipose tissue, thereby reversing diet-induced insulin resistance. Finally, we suggest that tumor growth alters liver-adipose tissue crosstalk that upregulates Fgf21, induces senescence, and negatively modulates lipids and carbohydrates metabolism even in caloric-restricted-fed mice.

Limited understanding exists regarding the association between daily total dietary nutrient intakes and immune-inflammation states in US adults exposed to various pathogens. This study sought to examine the correlation between nutrient intakes and immune-inflammation indicators and to assess their performance in distinguishing immune-inflammation states.

This study was derived from the National Health and Nutrition Examination Survey (NHANES), which included 33,804 participants aged 20 years or older between 2005 and 2018. Multivariable linear regression and restricted cubic spline regression were conducted to evaluate the association between nutrient intakes and immune-inflammation indicators. Receiver operating characteristic curve analysis was performed to evaluate the discriminatory performance of identified nutrients for various immune-inflammation states measured by the systemic immune-inflammation index (SII).

Ten key nutrients were significantly associated with immune-inflammation responses, including calcium, saturated fatty acid (SFA) 4:0, SFA 6:0, SFA 12:0, SFA 14:0, SFA 16:0, vitamin B2, total SFAs, retinol, and lutein + zeaxanthin, which show potential as dietary indicators. The area under the curve for discriminating various immune-inflammation states was improved by at least 0.03 compared with a model that included only covariates, with all P values <0.05 in the Delong tests, indicating a significant enhancement in model performance.

Ten nutrients, including calcium, various SFAs, vitamin B2, retinol, and lutein + zeaxanthin, exhibit significant association with SII and potential as dietary indicators for distinguishing between different immune-inflammation states in US adults with seropositivity to various viruses.

Conjugated fatty acids (CFAs) have been known for their anti-tumor activity. However, the mechanism of action remains unclear. Here, we identify CFAs as inducers of glutathione peroxidase 4 (GPX4) degradation through chaperone-mediated autophagy (CMA). CFAs, such as (10E,12Z)-octadecadienoic acid and α-eleostearic acid (ESA), induced GPX4 degradation, generation of mitochondrial reactive oxygen species (ROS) and lipid peroxides, and ultimately ferroptosis in cancer cell lines, including HT1080 and A549 cells, which were suppressed by either pharmacological blockade of CMA or genetic deletion of LAMP2A, a crucial molecule for CMA. Mitochondrial ROS were sufficient and necessary for CMA-dependent GPX4 degradation. Oral administration of an ESA-rich oil attenuated xenograft tumor growth of wild-type, but not that of LAMP2A-deficient HT1080 cells, accompanied by increased lipid peroxidation, GPX4 degradation and cell death. Our study establishes mitochondria as the key target of CFAs to trigger lipid peroxidation and GPX4 degradation, providing insight into ferroptosis-based cancer therapy.

Hospitalized COVID-19 patients exhibit diverse immune responses during acute infection, which are associated with a wide range of clinical outcomes. However, understanding these immune heterogeneities and their links to various clinical complications, especially long COVID, remains a challenge. In this study, we performed unsupervised subtyping of longitudinal multi-omics immunophenotyping in over 1,000 hospitalized patients, identifying two critical subtypes linked to mortality or mechanical ventilation with prolonged hospital stay and three severe subtypes associated with timely acute recovery. We confirmed that unresolved systemic inflammation and T-cell dysfunctions were hallmarks of increased severity and further distinguished patients with similar acute respiratory severity by their distinct immune profiles, which correlated with differences in demographic and clinical complications. Notably, one critical subtype (SubF) was uniquely characterized by early excessive inflammation, insufficient anticoagulation, and fatty acid dysregulation, alongside higher incidences of hematologic, cardiac, and renal complications, and an elevated risk of long COVID. Among the severe subtypes, significant differences in viral clearance and early antiviral responses were observed, with one subtype (SubC) showing strong early T-cell cytotoxicity but a poor humoral response, slower viral clearance, and greater risks of chronic organ dysfunction and long COVID. These findings provide crucial insights into the complex and context-dependent nature of COVID-19 immune responses, highlighting the importance of personalized therapeutic strategies to improve both acute and long-term outcomes.

Neurodegeneration is preeminent in many neurological diseases, and still a major burden we fail to manage in patient's care. Its pathogenesis is complicated, intricate, and far from being completely understood. Taking multiple sclerosis as an example, we propose that neurodegeneration is neither a cause nor a consequence by itself. Mitochondrial dysfunction, leading to energy deficiency and ion imbalance, plays a key role in neurodegeneration, and is partly caused by the oxidative stress generated by microglia and astrocytes. Nodal and paranodal disruption, with or without myelin alteration, is further involved. Myelin loss exposes the axons directly to the inflammatory and oxidative environment. Moreover, oligodendrocytes provide a singular metabolic and trophic support to axons, but do not emerge unscathed from the pathological events, by primary myelin defects and cell apoptosis or secondary to neuroinflammation or axonal damage. Hereby, trophic failure might be an overlooked contributor to neurodegeneration. Thus, a complex interplay between neuroinflammation, demyelination, and neurodegeneration, wherein each is primarily and secondarily involved, might offer a more comprehensive understanding of the pathogenesis and help establishing novel therapeutic strategies for many neurological diseases and beyond.

Female consumption of a high-fat diet (HFD) may cause fertility issues and affects offspring development.

Evaluate the acute maternal preconception intake of a HFD on the fertility and reproduction parameters of breeding females; and on the somatic parameters and reflex ontogeny of male offspring.

Twenty-four rats were randomized into control (PC; n=12) and high-fat diet group (PHF; n=12) that consumed their respective diets during the 23-day preconception period. After that, 6 rats per group underwent oral glucose tolerance and insulin tolerance tests and were euthanized. The remaining rats were mated, during gestation and lactation, both groups ate a control diet. After birth, the male offspring's somatic parameters and reflexes were assessed.

The preconception diet caused dyslipidemia in the PHF. The PHF uterus exhibited a higher SFA (50.74 ± 0.32 %), a lower PUFA concentration (35.59 ± 0.33 %), and an increase in arachidonic acid (2.48 ± 0.03 %). PHF rats had hypertrophy in the endometrium, and ovaries with a higher quantity of corpora albicans and immature primordial follicles. The offspring of PHF rats had greater weight (6.70 ± 0.82 g), nasal-anal length (4.93± 0.27 cm), and tail length (1.74 ± 0.12 cm) on the first day of life, and had improved righting reflex, but delayed negative geotaxis reflex.

An acute maternal preconception HFD induced a pro-inflammatory fatty acid profile and changed structure in uterus, altered ovarian follicle profile. Also, potential interference in the size of the pups at birth and in brain development of male offspring.

Neonatal rats that receive sucrose during a critical postnatal period (CP, days 12 to 28) develop hypertension by the time they reach adulthood. Inflammation might contribute to changes during this period and could be associated with variations in the vascular smooth muscle (VSMC) phenotype.

We studied changes in inflammatory pathways that could underlie the expression of the secretory phenotype in the VSMC in the thoracic aorta of rats that received sucrose during CP.

We analyzed histological changes in the aorta and the expression of the COX-2, TLR4, iNOS, eNOS, MMP-2 and -9, and β- and α-actin, the quantities of TNF-α, IL-6, and IL-1β using ELISA, and the levels of fatty acids using gas chromatography.

The aortic wall presented disorganization, decellularization, and wavy elastic fibers and an increase in the lumen area. The α- and β-actin expressions were decreased, while COX-2, TLR4, TNF-α, and the activity of IL-6 were increased. Oleic acid was increased in CP in comparison to the control group.

There is transient hypertension at the end of the CP that is accompanied by inflammation and a change in the phenotype of VSMC to the secretory phenotype. The inflammatory changes could act as epigenetic signals to determine the development of hypertension when animals reach adulthood.

Sacha Inchi (Plukenetia volubilis L) (SI) is a traditional natural medicine from tropical rainforests of Amazon region in South America. As a raw material for edible oil, it has various pharmacological effects such as antioxidant, anti-inflammatory, hypolipidemia, and blood pressure lowering, which have attracted increasing attentions of pharmacists. This has prompted researchers to explore its pharmacological effects for potential applications in certain diseases. Among these, the study of its anti-inflammatory effects has become a particularly interesting topic, especially in rheumatoid arthritis (RA). RA is a systemic autoimmune disease, and often accompanied by chronic inflammatory reactions. Despite significant progress in its treatment, there is still an urgent need to find effective anti-RA drugs in regard to safety. This review summarizes the potential therapeutic effects of SI on RA by modulating gut microbiota, targeting inflammatory cells and pathways, and mimicking biologic antibody drugs, predicting the application prospects of SI in RA, and providing references for research aimed at using SI to treat RA.

Obesity and frailty are prevalent geriatric conditions that share some pathophysiological mechanisms and are associated with adverse clinical outcomes. The relationship between frailty, obesity, and polymorphism remains inadequately explored. Single nucleotide polymorphisms (SNPs) offer insights into genetic predispositions that may influence the development of both frailty and obesity.

We aimed at investigating whether SNPs associated with frailty also play a role in obesity. Data were collected from the FRASNET cross-sectional study, which included community-dwelling older individuals residing in Milan and nearby areas. Participants were recruited through random sampling. They underwent multidimensional geriatric assessments, which included the collection of blood samples for SNP analysis. Frailty was assessed using the frailty index, and body composition was evaluated using bioelectrical impedance analysis and anthropometric measures.

SNPs related to frailty and linked to the renin-angiotensin system (CYP11B2 rs1799998, AGT rs5051, and AGTR1 rs2131127), apoptosis pathways (CASP8 rs6747918), growth hormone signaling (GHR rs6180), inflammation (TLR4 rs5030717, CD33 rs3865444, and FN1 rs7567647), adducin (ADD3 rs3731566), and the 9p21-23 region (rs518054) were found to be associated with various measures of obesity in community-dwelling older adults.

Frailty-related SNPs contribute to obesity in community-dwelling older adults. We identified a novel association between adducin SNPs and visceral fat, which has not been previously reported. Detecting genetic predispositions to obesity and frailty early could aid in identifying individuals at risk, facilitating the adoption of preventive interventions. This represents an initial step toward promoting early intervention strategies.

Type 2 diabetes mellitus (T2DM) and cancer share common risk factors including obesity, inflammation, hyperglycemia, and hyperinsulinemia. High insulin levels activate the PI3K/Akt/mTOR signaling pathway promoting cancer cell growth, survival, proliferation, metastasis, and anti-apoptosis. The inhibition of the PI3K/Akt/mTOR signaling pathway for cancer remains a promising therapy; however, drug resistance poses a major problem in clinical settings resulting in limited efficacy of agents; thus, combination treatments with therapeutic inhibitors may solve the resistance to such agents. Understanding the metabolic link between diabetes and cancer can assist in improving the therapeutic strategies used for the management of cancer patients with diabetes and vice versa. This review provides an overview of shared molecular mechanisms between diabetes and cancer as well as discusses established and emerging therapeutic anti-cancer agents targeting the PI3K/Akt/mTOR pathway in cancer management.

Obesity continues to rise in prevalence and financial burden despite strong evidence linking it to an increased risk of developing several chronic diseases. Dopamine response and receptor density are shown to decrease under conditions of obesity. However, it is unclear if this could be a potential mechanism for treatment without drugs that have a potential for abuse. Therefore, the aim of this study was to investigate whether moderate-intensity exercise could reduce body weight gain and the associated decreases in dopamine signaling observed with high-fat diet-induced adiposity. We hypothesized that exercise would attenuate body weight gain and diet-induced inflammation in high-fat (HF)-fed mice, resulting in dopamine signaling (release and reuptake rate) comparable to sedentary, low-fat (LF)-fed counterparts. This hypothesis was tested using a mouse model of diet-induced obesity (DIO) and fast-scan cyclic voltammetry to measure evoked dopamine release and reuptake rates. Although the exercise protocol employed in this study was not sufficient to prevent significant body weight gain, there was an enhancement of dopamine signaling observed in female mice fed a HF diet that underwent treadmill running. Additionally, aerobic treadmill exercise enhanced the sensitivity to amphetamine (AMPH) in this same group of exercised, HF-fed females. The estrous cycle might influence the ability of exercise to enhance dopamine signaling in females, an effect not observed in male groups. Further research into females by estrous cycle phase, in addition to determining the optimal intensity and duration of aerobic exercise, are logical next steps.

Obesity poses a significant global health challenge, necessitating effective prevention and treatment strategies. Exercise and diet are recognized as pivotal interventions in combating obesity. This study reviews the literature concerning the impact of exercise-induced cytokines, dietary factors, and inflammation on adipose tissue metabolism, shedding light on potential pathways for therapeutic intervention.

A comprehensive review of relevant literature was conducted to elucidate the role of exercise-induced cytokines, including interleukin-6 (IL-6), interleukin-15 (IL-15), brain-derived neurotrophic factor (BDNF), irisin, myostatin, fibroblast growth factor 21 (FGF21), follistatin (FST), and angiopoietin-like 4 (ANGPTL4), in adipose tissue metabolism. Various databases were systematically searched using predefined search terms to identify relevant studies. Articles selected for inclusion underwent thorough analysis to extract pertinent data on the mechanisms underlying the influence of these cytokines on adipose tissue metabolism.

Exercise-induced cytokines exert profound effects on adipose tissue metabolism, influencing energy expenditure (EE), thermogenesis, fat loss, and adipogenesis. For instance, IL-6 activates AMP-activated protein kinase (AMPK), promoting fatty acid oxidation and reducing lipogenesis. IL-15 upregulates peroxisome proliferator-activated receptor delta (PPARδ), stimulating fatty acid catabolism and suppressing lipogenesis. BDNF enhances AMPK-dependent fat oxidation, while irisin induces the browning of white adipose tissue (WAT), augmenting thermogenesis. Moreover, myostatin, FGF21, FST, and ANGPTL4 each play distinct roles in modulating adipose tissue metabolism, impacting factors such as fatty acid oxidation, adipogenesis, and lipid uptake. The elucidation of these pathways offers valuable insights into the complex interplay between exercise, cytokines, and adipose tissue metabolism, thereby informing the development of targeted obesity management strategies.

Understanding the mechanisms by which exercise-induced cytokines regulate adipose tissue metabolism is critical for devising effective obesity prevention and treatment modalities. Harnessing the therapeutic potential of exercise-induced cytokines, in conjunction with dietary interventions, holds promise for mitigating the global burden of obesity. Further research is warranted to delineate the precise mechanisms underlying the interactions between exercise, cytokines, and adipose tissue metabolism.

The association between omega-3 fatty acids (O3FA) and celiac disease lacks sufficient investigation.

Utilizing data gleaned from the 2009 to 2014 National Health and Nutrition Examination Survey (NHANES), this research comprises a sample of 13 403 adults, each aged 20 years and above. We conducted a multivariable logistic regression analysis to assess the association between dietary intake of O3FA and celiac disease. Subsequently, a two-sample Mendelian randomization was performed to estimate the unconfounded causal relationship between serum O3FA and celiac disease. The principal analytical strategy utilized the inverse-variance weighted methodology.

In this cross-sectional study, 48 occurrences (0.36%) of celiac disease were encompassed. In the multivariable model, there was no association between dietary intake of O3FA and cases of celiac disease (odds ratio: 1.12, 95% confidence interval: 0.47-2.66, P  = 0.792). However, serum levels of O3FA determined by genetic assay were correlated with celiac disease (inverse-variance weighted, β = 0.2439, P  = 0.0287), with no evidence of horizontal pleiotropy ( P  = 0.3689).

The dietary consumption of O3FA did not exhibit an association with the risk of celiac disease in this cross-sectional investigation. However, a correlation between celiac disease and serum levels of O3FA was observed in the Mendelian randomization. Further investigations, including human clinical trials, are warranted.

Metabolic dysfunction-associated steatotic liver disease (MASLD) encompasses metabolic dysfunction-associated fatty liver (MASL) and metabolic dysfunction-associated steatohepatitis (MASH), with MASH posing a risk of progression to cirrhosis and hepatocellular carcinoma (HCC). The global prevalence of MASLD is estimated at approximately a quarter of the population, with significant healthcare costs and implications for liver transplantation. The pathogenesis of MASLD involves intrahepatic liver cells, extrahepatic components, and immunological aspects, particularly the involvement of macrophages. Hepatic macrophages are a crucial cellular component of the liver and play important roles in liver function, contributing significantly to tissue homeostasis and swift responses during pathophysiological conditions. Recent advancements in technology have revealed the remarkable heterogeneity and plasticity of hepatic macrophage populations and their activation states in MASLD, challenging traditional classification methods like the M1/M2 paradigm and highlighting the coexistence of harmful and beneficial macrophage phenotypes that are dynamically regulated during MASLD progression. This complexity underscores the importance of considering macrophage heterogeneity in therapeutic targeting strategies, including their distinct ontogeny and functional phenotypes. This review provides an overview of macrophage involvement in MASLD progression, combining traditional paradigms with recent insights from single-cell analysis and spatial dynamics. It also addresses unresolved questions and challenges in this area.

This study aimed to identify and quantify free fatty acids (FFAs), secretory phospholipase A2 group IIa (sPLA2-IIa) and cytosolic phospholipase A2 (cPLA2) in serum of superior limbic keratoconjunctivitis (SLK) patients and explored the association between FFAs, sPLA2-IIa and cPLA2 variations and SLK. Targeted metabolomic analysis of FFAs in serum was performed by gas chromatography tandem mass spectrometry (GC-MS/MS) analysis on 16 SLK patients (43.88 ± 7.88 years; female: 62.50%) and 25 healthy controls (43.12 ± 7.88 years; female: 64.00%). Qualitative and absolute quantitative results of FFAs were obtained and classified according to gender and thyroid tests. Differential lipid metabolites, metabolomic pathways and biomarkers were further evaluated. The serum sPLA2-IIa and cPLA2 were determined by enzyme linked immunosorbent assay (ELISA). Among 40 FFAs identified, 6 FFAs showed significant changes (P < 0.05) in SLK patients, including 4 decreased and 2 increased. They were mainly related to unsaturated fatty acid biosynthesis, α-linolenic acid and linoleic acid metabolism, and fatty acid biosynthesis. When dividing the data by gender or abnormal thyroid tests, some comparable FFAs alterations displayed in SLK patients. The ROC analysis revealed that the AUC values of linoleic acid, γ-linolenic acid, cis-8,11,14-eicosatrienoic acid, stearic acid, and palmitic acid, were all greater than 0.8. The serum concentrations of sPLA2-IIa and cPLA2 in patients with SLK were significantly higher than that in healthy controls. Lipidomics disturbance might be the potential mechanism of SLK. Serum FFA biomarkers associated with SLK have potential for the diagnosis and treatment of the disease.

Non-alcoholic fatty liver disease (NAFLD) has emerged as the most prevalent chronic liver disease globally. Non-alcoholic steatohepatitis (NASH) represents an extremely progressive form of NAFLD, which, without timely intervention, may progress to cirrhosis or hepatocellular carcinoma. Presently, a definitive comprehension of the pathogenesis of NAFLD/NASH eludes us, and pharmacological interventions targeting NASH specifically remain constrained. The aetiology of NAFLD encompasses a myriad of external factors including environmental influences, dietary habits and gender disparities. More significantly, inter-organ and cellular interactions within the human body play a role in the development or regression of the disease. In this review, we categorize the influences affecting NAFLD both intra- and extrahepatically, elaborating meticulously on the mechanisms governing the onset and progression of NAFLD/NASH. This exploration delves into progress in aetiology and promising therapeutic targets. As a metabolic disorder, the development of NAFLD involves complexities related to nutrient metabolism, liver-gut axis interactions and insulin resistance, among other regulatory functions of extraneous organs. It further encompasses intra-hepatic interactions among hepatic cells, Kupffer cells (KCs) and hepatic stellate cells (HSCs). A comprehensive understanding of the pathogenesis of NAFLD/NASH from a macroscopic standpoint is instrumental in the formulation of future therapies for NASH.

Lipid mediators have been suggested to play important roles in the pathogenesis of rheumatoid arthritis (RA). Lipidomics has recently allowed for the comprehensive analysis of lipids and has revealed the potential of lipids as biomarkers for the early diagnosis of RA and prediction of therapeutic responses. However, the relationship between disease activity and the lipid profile in RA remains unclear. In the present study, we performed a plasma lipidomic analysis of 278 patients with RA during treatment and examined relationships with disease activity using the Disease Activity Score in 28 joints (DAS28)-erythrocyte sedimentation rate (ESR). In all patients, five lipids positively correlated and seven lipids negatively correlated with DAS28-ESR. Stearic acid [FA(18:0)] (r = -0.45) and palmitic acid [FA(16:0)] (r = -0.38) showed strong negative correlations. After adjustments for age, body mass index (BMI), and medications, stearic acid, palmitic acid, bilirubin, and lysophosphatidylcholines negatively correlated with disease activity. Stearic acid inhibited osteoclast differentiation from peripheral blood monocytes in in vitro experiments, suggesting its contribution to RA disease activity by affecting bone metabolism. These results indicate that the lipid profile correlates with the disease activity of RA and also that some lipids may be involved in the pathogenesis of RA.

The metabolic network's primary sources of free fatty acids (FFAs) are long- and medium-chain fatty acids of triglyceride origin and short-chain fatty acids produced by intestinal microorganisms through dietary fibre fermentation. Recent studies have demonstrated that FFAs not only serve as an energy source for the body's metabolism but also participate in regulating arterial function. Excess FFAs have been shown to lead to endothelial dysfunction, vascular hypertrophy, and vessel wall stiffness, which are important triggers of arterial hypertension and atherosclerosis. Nevertheless, free fatty acid receptors (FFARs) are involved in the regulation of arterial functions, including the proliferation, differentiation, migration, apoptosis, inflammation, and angiogenesis of vascular endothelial cells (VECs) and vascular smooth muscle cells (VSMCs). They actively regulate hypertension, endothelial dysfunction, and atherosclerosis. The objective of this review is to examine the roles and heterogeneity of FFAs and FFARs in the regulation of arterial function, with a view to identifying the points of intersection between their actions and providing new insights into the prevention and treatment of diseases associated with arterial dysfunction, as well as the development of targeted drugs.

Inflammatory bowel disease (IBD) is a chronic disease that includes Crohn's disease (CD) and ulcerative colitis (UC). Although genome-wide association studies (GWASs) have identified many relevant genetic risk loci, the impact of these loci on protein abundance and their potential utility as clinical therapeutic targets remain uncertain. Therefore, this study aimed to investigate the pathogenesis of IBD and identify effective therapeutic targets through a comprehensive and integrated analysis. We systematically integrated GWAS data related to IBD, UC and CD (N = 25,305) by the study of de Lange KM with the human blood proteome (N = 7213) by the Atherosclerosis Risk in Communities (ARIC) study. Proteome-wide association study (PWAS), mendelian randomisation (MR) and Bayesian colocalisation analysis were used to identify proteins contributing to the risk of IBD. Integrative analysis revealed that genetic variations in IBD, UC and CD affected the abundance of five (ERAP2, RIPK2, TALDO1, CADM2 and RHOC), three (VSIR, HGFAC and CADM2) and two (MST1 and FLRT3) cis-regulated plasma proteins, respectively (P < 0.05). Among the proteins identified via Bayesian colocalisation analysis, CADM2 was found to be an important common protein between IBD and UC. A drug and five druggable target genes were identified from DGIdb after Bayesian colocalisation analysis. Our study's findings from genetic and proteomic approaches have identified compelling proteins that may serve as important leads for future functional studies and potential drug targets for IBD (UC and CD).

Medium-chain acyl-CoA dehydrogenase deficiency (MCADD) is the most prevalent mitochondrial fatty acid β-oxidation disorder. In this study, we assessed the variability of the lipid profile in MCADD by analysing plasma samples obtained from 25 children with metabolically controlled MCADD (following a normal diet with frequent feeding and under l-carnitine supplementation) and 21 paediatric control subjects (CT). Gas chromatography-mass spectrometry was employed for the analysis of esterified fatty acids, while high-resolution C18-liquid chromatography-mass spectrometry was used to analyse lipid species. We identified a total of 251 lipid species belonging to 15 distinct lipid classes. Principal component analysis revealed a clear distinction between the MCADD and CT groups. Univariate analysis demonstrated that 126 lipid species exhibited significant differences between the two groups. The lipid species that displayed the most pronounced variations included triacylglycerols and phosphatidylcholines containing saturated and monounsaturated fatty acids, specifically C14:0 and C16:0, which were found to be more abundant in MCADD. The observed changes in the plasma lipidome of children with non-decompensated MCADD suggest an underlying alteration in lipid metabolism. Therefore, longitudinal monitoring and further in-depth investigations are warranted to better understand whether such alterations are specific to MCADD children and their potential long-term impacts.

Oral nutritional supplements (ONSs) are crucial for supporting the nutritional needs of pediatric populations, particularly those with medical conditions or dietary deficiencies. Bioactive compounds within ONSs play a pivotal role in enhancing health outcomes by exerting various physiological effects beyond basic nutrition. However, the comprehensive understanding of these bioactives in pediatric ONSs remains elusive.

This systematic narrative review aims to critically evaluate the existing literature concerning bioactive compounds present in oral nutritional supplements from a pediatric standpoint, focusing on their types, sources, bioavailability, physiological effects, and clinical implications.

A systematic search was conducted across the major academic databases, including PubMed, Scopus, and Web of Science, employing predefined search terms related to oral nutritional supplements, bioactives, and pediatrics. Studies published between 2013 and 2024 were considered eligible for inclusion. Data extraction and synthesis were performed according to the PRISMA guidelines.

The initial search yielded 558 of articles, of which 72 met the inclusion criteria. The included studies encompassed a diverse range of bioactive compounds present in pediatric ONS formulations, including, but not limited to, vitamins, minerals, amino acids, prebiotics, probiotics, and phytonutrients. These bioactives were sourced from various natural and synthetic origins and were found to exert beneficial effects on growth, development, immune function, gastrointestinal health, cognitive function, and overall well-being in pediatric populations. However, variations in bioavailability, dosing, and clinical efficacy were noted across different compounds and formulations.

Bioactive compounds in oral nutritional supplements offer promising avenues for addressing the unique nutritional requirements and health challenges faced by pediatric populations. However, further research is warranted to elucidate the optimal composition, dosage, and clinical applications of these bioactives in pediatric ONS formulations. A deeper understanding of these bioactive compounds and their interplay with pediatric health may pave the way for personalized and effective nutritional interventions in pediatric clinical practice.

Recent literature extensively investigates the crucial role of energy metabolism in determining the inflammatory response and polarization status of macrophages. This rapidly expanding area of research highlights the importance of understanding the link between energy metabolism and macrophage function. The metabolic pathways in macrophages are intricate and interdependent, and they can affect the polarization of macrophages. Previous studies suggested that glucose flux through cytosolic glycolysis is necessary to trigger pro-inflammatory phenotypes of macrophages, and fatty acid oxidation is crucial to support anti-inflammatory responses. However, recent studies demonstrated that this understanding is oversimplified and that the metabolic control of macrophage polarization is highly complex and not fully understood yet. How the metabolic flux through different metabolic pathways (glycolysis, glucose oxidation, fatty acid oxidation, ketone oxidation, and amino acid oxidation) is altered by obesity- and type 2 diabetes (T2D)-associated insulin resistance is also not fully defined. This mini-review focuses on the impact of insulin resistance in obesity and T2D on the metabolic flux through the main metabolic pathways in macrophages, which might be linked to changes in their inflammatory responses. We closely evaluated the experimental studies and methodologies used in the published research and highlighted priority research areas for future investigations.

It has been well documented that n-3 polyunsaturated fatty acids (n-3 PUFA) can alleviate inflammation caused by Escherichia coli (E. coli) lipopolysaccharides (LPS), the etiologic agents that causing yellow or white dysentery in young pigs. However, it remains unclear whether the increase in n-3 PUFA availability could enhance the ability of nursery pigs to resist invasion by E. coli. LPS. Twenty-four 21-day-old female piglets, each two of them from the same sow fed the beef tallow (BT) or fish oil (FO) diets, were allocated into four treatment groups: BT-CON, piglets from the BT-fed sows and intraperitoneally injected with saline (9 g/L); BT-LPS, piglets from the BT-fed sows and injected with LPS (100 μg/kg body weight); FO-CON, piglets from the FO-fed sows and injected with saline; FO-LPS, piglets from the FO-fed sows and injected with LPS. Following 2 h of LPS challenge, the magnitudes of increase in body temperature approached to a marked (p < 0.01) difference between the BT-CON and BT-LPS piglets, whereas the dramatic (p < 0.01) difference between the FO-CON and FO-LPS piglets was only observed at 4 h post LPS challenge. The body temperature averaged across the time points evaluated was about 0.2°C lower (p < 0.05) in the FO group than in the BT group. The FO group had lower (p < 0.05) mean corpuscular hemoglobin concentration, lower increase in serum interleukin (IL)-1β (p < 0.10) and IL-8 (p < 0.05) levels, higher (p < 0.01) serum albumin concentration, and higher (p = 0.10) ratios of jejunum villus height to crypt depth than the BT group. The FO group had much higher (p < 0.0001) ileal content of C20:5n3, C24:0, and C22:6n3, which were 2-4 times the content of the BT group. LPS challenge resulted in decreased (p < 0.05) intestinal C20:1 and C20:5n3 content, and the decrease (p < 0.05) in intestinal C20:3n6 and C24:1 content was observed in the BT-LPS piglets rather than in the FO-LPS piglets. Taken together, this study indicated that maternal consumption of fish oil protected breast-fed piglets against E. coli LPS-induced damage through reshaping of intestinal fatty acids profile, which sheds new light on the development of nutritional strategies to enhance the ability of young pigs to resist E. coli invasion.

Immunometabolism is an emerging field at the intersection of immunology and metabolism. Immune cell activation plays a critical role in the pathogenesis of cardiovascular diseases and is integral for regeneration during cardiac injury. We currently possess a limited understanding of the processes governing metabolic interactions between immune cells and cardiomyocytes. The impact of this intercellular crosstalk can manifest as alterations to the steady state flux of metabolites and impact cardiac contractile function. Although much of our knowledge is derived from acute inflammatory response, recent work emphasizes heterogeneity and flexibility in metabolism between cardiomyocytes and immune cells during pathological states, including ischemic, cardiometabolic, and cancer-associated disease. Metabolic adaptation is crucial because it influences immune cell activation, cytokine release, and potential therapeutic vulnerabilities. This review describes current concepts about immunometabolic regulation in the heart, focusing on intercellular crosstalk and intrinsic factors driving cellular regulation. We discuss experimental approaches to measure the cardio-immunologic crosstalk, which are necessary to uncover unknown mechanisms underlying the immune and cardiac interface. Deeper insight into these axes holds promise for therapeutic strategies that optimize cardioimmunology crosstalk for cardiac health.

Psoriasis is a chronic systemic disease with a multifaceted pathomechanism and immunological basis, with the presence of inflammatory skin lesions and joint ailments. Diseases accompanying psoriasis include metabolic and cardiovascular disorders. It has been suggested that inflammation is involved in the development of each of these conditions. The main objective of this study was to analyse the fatty acid profile, including polyunsaturated fatty acids, in the erythrocyte membranes of patients suffering from psoriasis. A total of 58 adult patients of the Department of Skin and Venereal Diseases of the Pomeranian Medical University in Szczecin, suffering from psoriasis, were qualified for this study. The patients had undergone an interview and physical examination, during which the severity of psoriasis was assessed. All patients had their weight and height measured to assess their body mass index (BMI). After 3 months of treatment, biochemical parameters (ALT, AST, total cholesterol) and inflammatory markers (CRP) in the blood were assessed. In addition, the isolation of fatty acids (PUFAs, SFAs, MUFAs) from erythrocyte membranes and the qualitative and quantitative analysis of their profile using a gas chromatograph were carried out. In patients with severe psoriasis requiring systemic treatment, an altered profile of fatty acids in erythrocyte membranes was found, including a significantly lower concentration of polyunsaturated fatty acids (omega-3), which have an anti-inflammatory effect; a significantly higher concentration of saturated fatty acids; and a decreased concentration of oleic acid (omega-9), compared to the results obtained in patients with less severe psoriasis receiving topical treatment. In patients with psoriasis and BMI ≥ 25, significantly higher concentrations of AST and ALT in the blood and significantly higher concentrations of pro-inflammatory arachidonic acid in erythrocyte membranes were found. Elevated concentrations of saturated (R = 0.31) and monounsaturated fatty acids (R = 0.29) may correlate with a greater severity of psoriasis.

Polyunsaturated fatty acids such as DHA have known anti-inflammatory properties. The therapeutic implication highlights the importance of accurate serum measurements. Sample preservation is challenging when performed parallel to the clinical obligations. Impact of time between sample collection and processing regarding concentration alterations of fatty acids in human blood remains to be elucidated. Therefore, more information is required with respect to the stability and storage options in the context of potential degradation and concentration changes. This study investigates the stability of DHA in serum samples over time, given the challenges of timely sample analysis in clinical settings. Blood samples from three patients were collected and stored at +4 °C. Concentrations were analysed between 6 h and 7 days post-collection. Our data indicate that DHA concentrations remained unchanged during the observational period. Our results suggest that storage duration up to 7 days before sample processing does not affect accuracy of the results. DHA measurements is crucial for ongoing and future research in cardiovascular and inflammatory diseases. Our results reveal that DHA stability remains consistent over one week. This information is important for further clinical studies investigating PUFA concentrations, providing researches the option to postpone processing of samples if required along the clinical obligations.