Background: Gastric cancer (GC) continues to be one of the leading causes of cancer-related deaths globally. Diet significantly influences the incidence and progression of GC. However, the relationship between dietary intake and GC is inconsistent. Methods: A study was conducted with adults who participated in the National Health and Nutrition Examination Survey (NHANES) from 2003 to 2016 to investigate possible associations between 32 dietary factors and GC. To further detect potential causal relationships between these dietary factors and the risk of GC, a two-sample Mendelian randomization (MR) analysis was conducted. The primary method employed was the inverse variance weighted (IVW) analysis, and its results were further validated by four other methods. Results: Of the 35,098 participants surveyed, 20 had a history of GC. Based on the results of weighted logistic multivariate analysis, it was observed that there was a positive correlation between total fat intake [odds ratio (OR) = 1.09, 95% confidence interval (CI): (1.01-1.17), p = 0.03] and GC as well as negative association of dietary monounsaturated fatty acids (MUFAs) intake [OR = 0.83, 95% CI: (0.76-0.92), p < 0.001]. Further evaluations of the odds of GC across the quartiles of dietary MUFAs showed that the top quartile of total MUFA intake was associated with a lower likelihood of GC in three different models [model1: OR = 0.03, 95% CI: (0.00-0.25), p < 0.01; model2: OR = 0.04, 95% CI: (0.00-0.38), p = 0.01; model3: OR = 0.04, 95% CI: (0.00-0.40), p = 0.01]. For the MR analyses, genetic instruments were selected from the IEU Open GWAS project; IVW analysis showed that GC risk was not associated with MUFAs [OR = 0.82, 95% CI: (0.59-1.14), p = 0.23] or the ratio of MUFAs to total fatty acids [OR = 1.00, 95% CI: (0.75-1.35), p = 0.98]. Similar results were observed when using the other MR methods. Conclusion: The NHANES study revealed that consuming MUFAs was linked to a lower risk of GC, although the results of MR analyses do not provide evidence of a causal relationship. Additional research is therefore necessary to clarify these findings.

BACKGROUND: Targeting ferroptosis has been identified as a promising approach for the development of cancer therapies. Monounsaturated fatty acid (MUFA) is a type of lipid that plays a crucial role in inhibiting ferroptosis. Ficolin 3 (FCN3) is a component of the complement system, serving as a recognition molecule against pathogens in the lectin pathway. Recent studies have reported that FCN3 demonstrates inhibitory effects on the progression of certain tumors. However, whether FCN3 can modulate lipid metabolism and ferroptosis remains largely unknown.
METHODS: Cell viability, BODIPY-C11 staining, and MDA assay were carried out to detect ferroptosis. Primary hepatocellular carcinoma (HCC) and xenograft models were utilized to investigate the effect of FCN3 on the development of HCC in vivo. A metabonomic analysis was conducted to assess alterations in intracellular and HCC intrahepatic lipid levels.
RESULTS: Our study elucidates a substantial decrease in the expression of FCN3, a component of the complement system, leads to MUFA accumulation in human HCC specimens and thereby significantly promotes ferroptosis resistance. Overexpression of FCN3 efficiently sensitizes HCC cells to ferroptosis, resulting in the inhibition of the oncogenesis and progression of both primary HCC and subcutaneous HCC xenograft. Mechanistically, FCN3 directly binds to the insulin receptor β (IR-β) and its pro-form (pro-IR), inhibiting pro-IR cleavage and IR-β phosphorylation, ultimately resulting in IR-β inactivation. This inactivation of IR-β suppresses the expression of sterol regulatory element binding protein-1c (SREBP1c), which subsequently suppresses the transcription of genes related to de novo lipogenesis (DNL) and lipid desaturation, and consequently downregulates intracellular MUFA levels.
CONCLUSIONS: These findings uncover a novel regulatory mechanism by which FCN3 enhances the sensitivity of HCC cells to ferroptosis, indicating that targeting FCN3-induced ferroptosis is a promising strategy for HCC treatment.

OBJECTIVE: Exposure of adipocytes to \'cool\' temperatures often found in the periphery of the body induces expression of Stearoyl-CoA Desaturase-1 (Scd1), an enzyme that converts saturated fatty acids to monounsaturated fatty acids. The goal of this study is to further investigate the roles of Scd in adipocytes.
METHODS: In this study, we employed Scd1 knockout cells and mouse models, along with pharmacological Scd1 inhibition to dissect the enzyme\'s function in adipocyte physiology.
RESULTS: Our study reveals that production of monounsaturated lipids by Scd1 is necessary for fusion of autophagosomes to lysosomes and that with a Scd1-deficiency, autophagosomes accumulate. In addition, Scd1-deficiency impairs lysosomal and autolysosomal acidification resulting in vacuole accumulation and eventual cell death. Blocking autophagosome formation or supplementation with monounsaturated fatty acids maintains vitality of Scd1-deficient adipocytes.
CONCLUSIONS: This study demonstrates the indispensable role of Scd1 in adipocyte survival, with its inhibition in vivo triggering autophagy-dependent cell death and its depletion in vivo leading to the loss of bone marrow adipocytes.

Atherosclerosis is a key risk factor for developing cardiovascular diseases (CVDs). Flow-mediated dilation (FMD), which reflects vascular reactivity, as well as pulse wave velocity (PWV) and augmentation index (AIx), both markers of arterial stiffness, have emerged as noninvasive, subclinical atherosclerotic markers for the early stages of altered vascular function. In addition to the long-term effects of diet, postprandial processes have been identified as important determinants of CVD risk, and evidence suggests an acute effect of fat quantity and fatty acid (FA) composition on vascular function. However, robust analyses of this association are lacking, especially concerning parameters of arterial stiffness. Therefore, we carried out a systematic literature search in PubMed, Scopus, and the Cochrane Library to investigate the impact of fat quantity and FA composition of meals on postprandial vascular function. Postprandial studies measuring FMD, PWV, and/or AIx in healthy adults and subjects with increased CVD risk (e.g., those with hypercholesterolemia or metabolic syndrome) were analyzed. In total, 24 articles were included; 9 studies focused on the effect of high-fat meals compared with control; and 15 studies investigated the effects of different fat sources. We found that consumption of a high-fat meal causes a reduction in FMD (decrease in vasodilation) and AIx (decrease in arterial stiffness). For eicosapentaenoic acid/docosahexaenoic acid (from fish oil), postprandial assessment (FMD and AIx) indicates a beneficial effect on vascular function. There is limited evidence of an influence of CVD risk on the vascular response to meals with varying fat doses or FA composition. However, meaningful conclusions were difficult to draw because of the large heterogeneity of the studies. Inconsistent results regarding both the impact of fat dose and FA composition on postprandial vascular function should be noted. We propose standardized methods for postprandial protocols to improve data quality in future studies. This review was registered in PROSPERO as CRD42022352986.

This article aims to study the different dietary fat types associated with obesity and coronary indices. A sample of 491 healthy adults was included in a cross-sectional manner. Dietary fats intake, obesity indices (conicity index (CI), body adiposity index (BAI), abdominal volume index (AVI), body roundness index (BRI), and weight-adjusted-waist index (WWI)), and cardiovascular indices (cardiometabolic index (CMI), lipid accumulation product (LAP), and atherogenic index of plasma (AIP)) were calculated and studied. Participants with an acceptable intake of omega-3 had a higher BRI score (1⋅90 ± 0⋅06 v. 1⋅70 ± 0⋅06). Participants with an unacceptable intake of cholesterol had a higher CI (1⋅31 ± 0⋅11 v. 1⋅28 ± 0⋅12; P = 0⋅011), AVI (20⋅24 ± 5⋅8 v. 18⋅33 ± 6⋅0; P < 0⋅001), BRI (2⋅00 ± 1⋅01 v. 1⋅70 ± 1⋅00; P = 0⋅003), WWI (11⋅00 ± 0⋅91 v. 10⋅80 ± 0⋅97; P = 0⋅032), and lower AIP (0⋅46 ± 0⋅33 v. 0⋅53 ± 0⋅33; P = 0⋅024). Total fat, saturated fat (SFA), and polyunsaturated fat (PUFA) intake had a significant moderate correlation with AVI and BRI. The monounsaturated fat (MUFA) intake had a significantly weak correlation with CI, AVI, BRI, WWI, and AIP. Cholesterol and omega-6 had weak correlations with all indices. Similar correlations were seen among male and female participants. The different types of fat intake significantly affected obesity and coronary indices, especially SFA and PUFA, as well as omega-3 and cholesterol. Gender and the dietary type of fat intake have a relationship to influence the indicators of both obesity and coronary indices.

Ferroptosis is a non-apoptotic form of cell death that can be triggered by inhibiting the system xc- cystine/glutamate antiporter or the phospholipid hydroperoxidase glutathione peroxidase 4 (GPX4). We have investigated how cell cycle arrest caused by stabilization of p53 or inhibition of cyclin-dependent kinase 4/6 (CDK4/6) impacts ferroptosis sensitivity. Here, we show that cell cycle arrest can enhance sensitivity to ferroptosis induced by covalent GPX4 inhibitors (GPX4i) but not system xc- inhibitors. Greater sensitivity to GPX4i is associated with increased levels of oxidizable polyunsaturated fatty acid-containing phospholipids (PUFA-PLs). Higher PUFA-PL abundance upon cell cycle arrest involves reduced expression of membrane-bound O-acyltransferase domain-containing 1 (MBOAT1) and epithelial membrane protein 2 (EMP2). A candidate orally bioavailable GPX4 inhibitor increases lipid peroxidation and shrinks tumor volumes when combined with a CDK4/6 inhibitor. Thus, cell cycle arrest may make certain cancer cells more susceptible to ferroptosis in vivo.

Iron overload, characterized by accumulation of iron in tissues, induces a multiorgan toxicity whose mechanisms are not fully understood. Using cultured cell lines, Caenorhabditis elegans, and mice, we found that ferroptosis occurs in the context of iron-overload-mediated damage. Exogenous oleic acid protected against iron-overload-toxicity in cell culture and Caenorhabditis elegans by suppressing ferroptosis. In mice, oleic acid protected against FAC-induced liver lipid peroxidation and damage. Oleic acid changed the cellular lipid composition, characterized by decreased levels of polyunsaturated fatty acyl phospholipids and decreased levels of ether-linked phospholipids. The protective effect of oleic acid in cells was attenuated by GW6471 (PPAR-α antagonist), as well as in Caenorhabditis elegans lacking the nuclear hormone receptor NHR-49 (a PPAR-α functional homologue). These results highlight ferroptosis as a driver of iron-overload-mediated damage, which is inhibited by oleic acid. This monounsaturated fatty acid represents a potential therapeutic approach to mitigating organ damage in iron overload individuals.

Edible insects play an important role in human health and food security. Among those, the Giant water bug, Lethocerus indicus (Lep.& Ser.) is a widely used edible insect known for its aroma, flavor, and therapeutic purposes. In the present study, we investigated the nutritional profile, natural habitat, and feeding behavior of L. indicus in aquarium conditions. A comparative analysis of male and female insects\' aroma contents and fatty acid (FA) profiles was also conducted. A dry fried male insect yielded volatile oil of 0.96%/2 g body weight, whereas a dry fried female yielded 0.48%/5.36 g of body weight. In terms of lipids, fresh male insects had 0.15%/5.42 g of body weight and fresh female insects had 0.28%/9.48 g of body weight. There are 24 volatile compounds specific to males, 37 specific to females, and 13 commons to both were identified. 2-Hexen-1-ol, acetate, (Z)- which smells like banana, was prevalently found in males while 4-Octene, 2,6-dimethyl-, [S-(Z)] was prevalently found in female insects. Fatty acids profile analysis detected 32 FA with 12 unique FA from males whereas 22 FA and 3 unique FA were identified from female insects. The SFA percentage present in males and females was 77.44% and 85.21%. Males had 6.78% MUFA content while females have 4.75%. Males have 18% PUFA content enriched with DHA, and EPA, while females had 10.04%. This study revealed that with the presence of a banana-like smell of volatile compound and more MUFA and PUFA in males, the native people of North-East India preferred male over female insects for entomophagy.

Avocado consumption is linked to better glucose homeostasis, but small associations suggest potential population heterogeneity. Metabolomic data capture the effects of food intake after digestion and metabolism, thus accounting for individual differences in these processes.
To identify metabolomic biomarkers of avocado intake and to examine their associations with glycemia.
Baseline data from 6224 multi-ethnic older adults (62% female) included self-reported avocado intake, fasting glucose and insulin, and untargeted plasma proton nuclear magnetic resonance metabolomic features (metabolomic data were available for a randomly selected subset; N = 3438). Subsequently, incident type 2 diabetes (T2D) was assessed over an ∼18 y follow-up period. A metabolome-wide association study of avocado consumption status (consumer compared with nonconsumer) was conducted, and the relationship of these features with glycemia via cross-sectional associations with fasting insulin and glucose and longitudinal associations with incident T2D was examined.
Three highly-correlated spectral features were associated with avocado intake at metabolome-wide significance levels (P < 5.3 ∗ 10-7) and combined into a single biomarker. We did not find evidence that these features were additionally associated with overall dietary quality, nor with any of 47 other food groups (all P > 0.001), supporting their suitability as a biomarker of avocado intake. Avocado intake showed a modest association only with lower fasting insulin (β = -0.07 +/- 0.03, P = 0.03), an association that was attenuated to nonsignificance when additionally controlling for body mass index (kg/m2). However, our biomarker of avocado intake was strongly associated with lower fasting glucose (β = -0.22 +/- 0.02, P < 2.0 ∗ 10-16), lower fasting insulin (β = -0.17 +/- 0.02, P < 2.0 ∗ 10-16), and a lower incidence of T2D (hazard ratio: 0.68; 0.63-074, P < 2.0 ∗ 10-16), even when adjusting for BMI.
Highly significant associations between glycemia and avocado-related metabolomic features, which serve as biomarkers of the physiological impact of dietary intake after digestion and absorption, compared to modest relationships between glycemia and avocado consumption, highlights the importance of considering individual differences in metabolism when considering diet-health relationships.

Ferroptosis is a non-apoptotic form of cell death characterized by iron-dependent lipid peroxidation. Ferroptosis can be induced by system xc- cystine/glutamate antiporter inhibition or by direct inhibition of the phospholipid hydroperoxidase glutathione peroxidase 4 (GPX4). The regulation of ferroptosis in response to system xc- inhibition versus direct GPX4 inhibition may be distinct. Here, we show that cell cycle arrest enhances sensitivity to ferroptosis triggered by GPX4 inhibition but not system xc- inhibition. Arrested cells have increased levels of oxidizable polyunsaturated fatty acid-containing phospholipids, which drives sensitivity to GPX4 inhibition. Epithelial membrane protein 2 (EMP2) expression is reduced upon cell cycle arrest and is sufficient to enhance ferroptosis in response to direct GPX4 inhibition. An orally bioavailable GPX4 inhibitor increased markers of ferroptotic lipid peroxidation in vivo in combination with a cell cycle arresting agent. Thus, responses to different ferroptosis-inducing stimuli can be regulated by cell cycle state.