High Saturated Fat Diet Research Articles

High-intensity interval training improves cardiomyocyte contractile function and myofilament sensitivity to intracellular Ca2+ in obese rats.

High-intensity interval training (HIIT) has shown significant results in addressing adiposity and risk factors associated with obesity. However, there are no studies that investigate the effects of HIIT on contractility and intracellular Ca2+ handling. The purpose of this study was to explore the impact of HIIT on cardiomyocyte contractile function and intracellular Ca2+ handling in rats in which obesity was induced by a saturated high-fat diet (HFD). Male Wistar rats were initially randomized into a standard diet and a HFD group. The experimental protocol spanned 23weeks, comprising the induction and maintenance of obesity (15weeks) followed by HIIT treatment (8weeks). Performance was assessed using the maximum oxygen consumption test ( ). Evaluation encompassed cardiac, adipose and skeletal muscle histology, as well as contractility and intracellular Ca2+ handling. HIIT resulted in a reduction in visceral area, an increase in , and an augmentation of gastrocnemius fibre diameter in obese subjects. Additionally, HIIT led to a decrease in collagen fraction, an increase in percentage shortening, and a reduction in systolic Ca2+/percentage shortening and systolic Ca2+/maximum shortening rates. HIIT induces physiological cardiac remodelling, enhancing the contractile function of cardiomyocytes and improving myofilament sensitivity to Ca2+ in the context of obesity. This approach not only enhances cardiorespiratory and physical performance but also reduces visceral area and prevents interstitial fibrosis.

The Influence of Strain and Sex on High Fat Diet-Associated Alterations of Dopamine Neurochemistry in Mice.

Objective: The objective of this study was to determine the influence of sex and strain on striatal and nucleus accumbens dopamine neurochemistry and dopamine-related behavior due to a high-saturated-fat diet (HFD). Methods: Male and female C57B6/J (B6J) and Balb/cJ (Balb/c) mice were randomly assigned to a control-fat diet (CFD) containing 10% kcal fat/g or a mineral-matched HFD containing 60% kcal fat/g for 12 weeks. Results: Intraperitoneal glucose tolerance testing (IPGTT) and elevated plus maze experiments (EPM) confirmed that an HFD produced marked blunting of glucose clearance and increased anxiety-like behavior, respectively, in male and female B6J mice. Electrically evoked dopamine release in the striatum and reuptake in the nucleus accumbens (NAc), as measured by ex vivo fast scan cyclic voltammetry, was reduced for HFD-fed B6J females. Impairment in glucose metabolism explained HFD-induced changes in dopamine neurochemistry for B6J males and, to a lesser extent, Balb/c males. The relative expressions of protein markers associated with the activation of microglia, ionized calcium binding adaptor molecule (Iba1) and cluster of differentiation molecule 11b (CD11b) in the striatum were increased due to an HFD for B6J males but were unchanged or decreased amongst HFD-fed Balb/c mice. Conclusions: Our findings demonstrate that strain and sex influence the insulin- and microglia-dependent mechanisms of alterations to dopamine neurochemistry and associated behavior due to an HFD.

BETA-HYDROXYBUTYRATE COUNTERACTS THE DELETERIOUS EFFECTS OF A SATURATED HIGH-FAT DIET ON SYNAPTIC AMPA RECEPTORS AND COGNITIVE PERFORMANCE.

The ketogenic diet, characterized by high fat and low carbohydrates, has gained popularity not only as a strategy for managing body weight but also for its efficacy in delaying cognitive decline associated with neurodegenerative diseases and the aging process. Since this dietary approach stimulates the liver's production of ketone bodies, primarily β-hydroxybutyrate (BHB), which serves as an alternative energy source for neurons, we investigated whether BHB could mitigate impaired AMPA receptor trafficking, synaptic dysfunction, and cognitive decline induced by metabolic challenges such as saturated fatty acids. Here, we observe that, in cultured primary cortical neurons, exposure to palmitic acid (200μM) decreased surface levels of glutamate GluA1-containing AMPA receptors, whereas unsaturated fatty acids, such as oleic acid and ω-3 docosahexaenoic acid (200μM), and BHB (5mM) increased them. Furthermore, BHB countered the adverse effects of palmitic acid on synaptic GluA1 levels in hippocampal neurons, as well as excitability and plasticity in hippocampal slices. Additionally, daily intragastric administration of BHB (100 mg/kg/day) for two months reversed cognitive impairment induced by a saturated high-fat diet (49% of calories from fat) in a mouse experimental model of obesity. In summary, our findings underscore the significant impact of fatty acids and ketone bodies on AMPA receptors abundance, synaptic function and neuroplasticity, shedding light on the potential use of BHB to delay cognitive impairments associated with metabolic diseases.

High Saturated Fat Diet Mediated Neurodegeneration in Drosophila melanogaster

High Saturated Fat Diet Mediated Neurodegeneration in Drosophila melanogaster

High-fat diet-negative impact on female fertility: from mechanisms to protective actions of antioxidant matrices.

Excessive calorie intake poses a significant threat to female fertility, leading to hormonal imbalances and reproductive challenges. Overconsumption of unhealthy fats exacerbates ovarian dysfunction, with an overproduction of reactive oxygen species causing oxidative stress, impairing ovarian follicle development and leading to irregular ovulation and premature ovarian failure. Interest in biological matrices with high antioxidant properties to combat diet-related oxidative stress has grown, as they contain various bioactive factors crucial for neutralizing free radicals potentially preventing female reproductive health. This systematic review evaluates the female reproductive impact of biological matrices in mitigating oxidative damages induced by over calory habits and, in particular, high fat diets. A comparative approach among mammalian models was utilized to interpret literature available data. This approach specifically investigates the antioxidant mechanisms of biological matrices on early and late ovarian folliculogenesis, under physiological and hormone-induced female reproductive cycle. Adhering to the PRISMA 2020 guidelines, only English-language publications from peer-reviewed international indexes were considered. The analysis of 121 publications meeting the inclusion criteria facilitated the identification of crucial components of biological matrices. These components, including carbocyclic sugars, phytonutrients, organosulfur compounds, and vitamins, were evaluated for their impact on ovarian follicle resilience, oocyte quality, and reproductive lifespan. The detrimental effects of oxidative stress on female fertility, particularly exacerbated by high saturated fat diets, are well-documented. In vivo studies across mammalian preclinical models have underscored the potential of antioxidants derived from biological matrices to mitigate diet-induced conditions. These antioxidants enhance steroidogenesis and ovarian follicle development, thereby improving oocyte quality. Additionally, discussions within these publications emphasized the clinical significance of these biological matrices, translating research findings into practical applications for female health. Further research is essential to fully exploit the potential of these matrices in enhancing female reproduction and mitigating the effects of diets rich in fatty acids. This requires intensified in vitro studies and comprehensive collection of in vivo data before clinical trials. The promotion of ovarian resilience offers promising avenues for enhancing understanding and advancing female reproductive health world-wide.

Assessing the impact of concurrent high-fructose and high-saturated fat diets on pediatric metabolic syndrome: A review.

High-saturated fat (HF) or high-fructose (HFr) consumption in children predispose them to metabolic syndrome (MetS). In rodent models of MetS, diets containing individually HF or HFr lead to a variable degree of MetS. Nevertheless, simultaneous intake of HF plus HFr have synergistic effects, worsening MetS outcomes. In children, the effects of HF or HFr intake usually have been addressed individually. Therefore, we have reviewed the outcomes of HF or HFr diets in children, and we compare them with the effects reported in rodents. In humans, HFr intake causes increased lipogenesis, hypertriglyceridemia, obesity and insulin resistance. On the other hand, HF diets promote low grade-inflammation, obesity, insulin resistance. Despite the deleterious effects of simultaneous HF plus HFr intake on MetS development in rodents, there is little information about the combined effects of HF plus HFr intake in children. The aim of this review is to warn about this issue, as individually addressing the effects produced by HF or HFr may underestimate the severity of the outcomes of Western diet intake in the pediatric population. We consider that this is an alarming issue that needs to be assessed, as the simultaneous intake of HF plus HFr is common on fast food menus.

Silicon as a Functional Meat Ingredient Improves Jejunal and Hepatic Cholesterol Homeostasis in a Late-Stage Type 2 Diabetes Mellitus Rat Model.

Silicon included in a restructured meat (RM) matrix (Si-RM) as a functional ingredient has been demonstrated to be a potential bioactive antidiabetic compound. However, the jejunal and hepatic molecular mechanisms by which Si-RM exerts its cholesterol-lowering effects remain unclear. Male Wistar rats fed an RM included in a high-saturated-fat high-cholesterol diet (HSFHCD) combined with a low dose of streptozotocin plus nicotinamide injection were used as late-stage type 2 diabetes mellitus (T2DM) model. Si-RM was included into the HSFHCD as a functional food. An early-stage TD2M group fed a high-saturated-fat diet (HSFD) was taken as reference. Si-RM inhibited the hepatic and intestinal microsomal triglyceride transfer protein (MTP) reducing the apoB-containing lipoprotein assembly and cholesterol absorption. Upregulation of liver X receptor (LXRα/β) by Si-RM turned in a higher low-density lipoprotein receptor (LDLr) and ATP-binding cassette transporters (ABCG5/8, ABCA1) promoting jejunal cholesterol efflux and transintestinal cholesterol excretion (TICE), and facilitating partially reverse cholesterol transport (RCT). Si-RM decreased the jejunal absorptive area and improved mucosal barrier integrity. Consequently, plasma triglycerides and cholesterol levels decreased, as well as the formation of atherogenic lipoprotein particles. Si-RM mitigated the dyslipidemia associated with late-stage T2DM by Improving cholesterol homeostasis. Silicon could be used as an effective nutritional approach in diabetic dyslipidemia management.

High Fat Feeding Blunts Skeletal Muscle Oxygen Mediated Blood Flow Responses in Healthy and Type 2 Diabetic Rats

Hypothesis: High fat diet feeding impairs microvascular blood flow responses to dynamic changes in local oxygen concentration ([O2]) in Sprague-Dawley (SD) and Zucker Diabetic Sprague-Dawley (ZDSD) rats. Methods: Seven-week-old male SD and ZDSD rats were fed either a standard chow (N = 7 SD, 5 ZDSD) or a high saturated fat diet (N = 8 SD, 6 ZDSD) for 7 weeks. At 14 weeks of age animals were anaesthetized, instrumented for systemic monitoring, and mechanically ventilated. The extensor digitorum longus muscle was blunt dissected and reflected over a gas exchange chamber imbedded in the stage of an inverted microscope. Microvascular blood flow responses to high and low [O2] challenges (7 – 12 %, and 7 – 2 %) and sequential changes in [O2] (7 – 12 – 2 – 7 %) were recorded at baseline and during hyperinsulinemic-euglycemic clamp. Gas conditions within the chamber were set at 7 % for a 1-minute baseline followed by 2 minutes at either 2 or 12 % O2. The 4-minute square wave oscillation consisted of 1 minute at each [O2] (7 – 12 – 2 – 7 %). Hyperinsulinemic-euglycemic clamp was achieved by simultaneous infusion of insulin (2 U/hr/kg) and variable rate of 50 % glucose until euglycemia was reached (5 - 7 mM blood glucose). Analysis of intravital videos was completed using custom MATLAB software. All animal protocols were approved by Memorial University’s Animal Care Committee. Results: Chow fed SD had significantly higher glucose infusion rates compared to high fat fed SD, chow fed ZDSD, and high fat fed ZDSD (28.11 ± 1.807 vs. 25.14 ± 1.18, 24.56 ± 2.78, 24.77 ± 2.43 mg/kg/min, p = 0.0429, 0.0305, 0.0323, respectively). Red blood cell (RBC) saturation significantly increased and decreased in all groups within 4 s following the increase and decrease in [O2], respectively. Chow fed SD had significant decrease in RBC supply rate (SR) in response to 12 % [O2] (10.41 ± 11.31 vs 7.44 ± 8.40 cells/s, p < 0.0001, τ = 15.85 s). In response to low [O2], significant increases in SR were measured in the chow fed SD and ZDSD groups (7.10 ± 8.76 vs 11.65 ± 11.36 cells/s, p < 0.0001, τ = 17.65 s, and 10.86 ± 13.62 vs 13.86 ± 14.69 cells/s, p < 0.0001, τ = 85.74 s, respectively). High fat fed SD and ZDSD had significant increases in RBC SR during 2 % [O2] (8.47 ± 9.75 vs 11.84 ± 12.11 cells/s, p < 0.0001, τ = 68.49 s, and 16.09 ± 18.12 vs 20.73 ± 21.92 cells/s, p < 0.0001, τ = 23.98 s). High fat fed ZDSD had higher, but not significantly different, baseline RBC SR compared to the chow fed ZDSD group. Chow fed SD were the only group to have an increase in RBC SR at low [O2] during hyperinsulinemic-euglycemic clamp (13.80 ± 17.78 vs 18.07 ± 20.25 cells/s, p = 0.0003, τ = 10.88 s). Conclusions: High fat feeding impairs the capillary blood flow response to local increases in [O2] in healthy and high fat fed T2D model rats. Chow fed ZDSD rats had slower capillary blood flow dynamics than the SD control group. Hyperinsulinemic-euglycemic clamp diminishes the O2 mediated blood flow response in 14-week-old SD and ZDSD rats fed a high fat diet. This project was supported by the Canadian Institute of Health Research through a project grant to GMF. Studentships were supported by Memorial University's School of Graduate Studies and the Faculty of Medicine. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Anti-steatotic effects of PPAR-alpha and gamma involve gut-liver axis modulation in high-fat diet-fed mice

AimTo evaluate the effects of PPARα and PPARγ activation (alone or in combination) on the gut-liver axis, emphasizing the integrity of the intestinal barrier and hepatic steatosis in mice fed a high saturated fat diet. MethodsMale C57BL/6J were fed a control diet (C) or a high-fat diet (HF) for ten weeks. Then, a four-week treatment started: HF-α (WY14643), HF-γ (low-dose pioglitazone), and HF-αγ (combination). ResultsThe HF caused overweight, insulin resistance, impaired gut-liver axis, and marked hepatic steatosis. Treatments reduced body mass, improved glucose homeostasis, and restored the gut microbiota diversity and intestinal barrier gene expression. Treatments also lowered the plasma lipopolysaccharide concentrations and favored beta-oxidation genes, reducing macrophage infiltration and steatosis in the liver. ConclusionTreatment with PPAR agonists modulated the gut microbiota and rescued the integrity of the intestinal barrier, alleviating hepatic steatosis. These results show that these agonists can contribute to metabolic-associated fatty liver disease treatment.

Study protocol for a 15-week randomised controlled trial assessing the independent effects of high-cholesterol and high-saturated fat diets on LDL cholesterol

IntroductionPrevious research has associated high dietary cholesterol intake with raised low-density lipoprotein cholesterol (LDL-C) and thus increased risk for cardiovascular disease (CVD). Emerging research suggests that it is saturated fat,...

Do markers of adiposity and glycaemia mediate the association between low carbohydrate diet and cardiovascular risk factors: findings from the UK National Diet and Nutrition Survey (NDNS) 2008–2016

ObjectivesTo examine the associations between low carbohydrate diet (LCD) and conventional cardiovascular risk factors and investigate whether these associations are mediated by body mass index (BMI), waist circumference (WC) and...

Dietary fat differentially modulates the response of bone marrow-derived macrophages to TLR4 and NOD2 agonists.

Consumption of diets high in fat has been linked to the development of obesity and related metabolic complications. Such associations originate from the enhanced, chronic, low-grade inflammation mediated by macrophages in response to translocated bacteria, bacterial products, or dietary constituents such as fatty acids (FAs). Nucleotide-binding Oligomerization Domain 2 (NOD2) senses muramyl dipeptide (MDP), a component of bacterial peptidoglycan. The inability to sense peptidoglycan through NOD2 has been demonstrated to lead to dysbiosis, increased bacterial translocation, inflammation and metabolic dysfunction. Currently, it is unknown how consumption of HFDs with different FA compositions might influence NOD2-dependent responses. In this study, we subjected WT mice to a control diet or to HFDs comprised of various ratios of unsaturated to saturated fats and determined the macrophage response to TLR4 and NOD2 agonists. A HFD with equal ratios of saturated and unsaturated fats enhanced subsequent responsiveness of macrophages to LPS but not to MDP. However, a high-unsaturated fat diet (HUFD) or a high-saturated fat diet (HSFD) both decreased the responsiveness to NOD2 agonists compared to that observed in control diet (CD) fed mice. These data suggest that dietary fatty acid composition can influence the subsequent macrophage responsiveness to bacterial products.

603-P: Changes in Insulin Resistance by Protein Source and Level of Saturated Fat—An Analysis of the Animal and Plant Protein and Cardiovascular Health (APPROACH) Trial

Background: Protein source and saturated fat (SFA) consumption may affect insulin resistance (IR). We aimed to assess IR using the ratio of triglycerides/HDL (TG/HDL) in the context of a randomized, controlled, crossover dietary intervention trial comparing red meat, white meat and non-meat protein sources at high and low SFA levels. Methods: Healthy men and women aged 21-65 y with BMI 20-35 kg/m2 were randomly assigned to 1 of 2 parallel arms (14% or 7% energy from SFA), and within each consumed diets with protein source derived primarily from red meat, white meat, and nonmeat sources for 4 weeks each in random order. We assessed protein source and log transformed TG/HDL ratio using generalized mixed models adjusting for diet order by level of SFA. A significant interaction was found between SFA and red meat intake (p<0.05). Results: Participants who completed all diets were included: 62 participants on high SFA diets (27 men, 30 women); 51 on low SFA (17 men, 34 women). Red and white meat consumption were each associated with lower log TG/HDL than non-meat protein consumption at high SFA but not low SFA (Table). There was no difference in log TG/HDL between white and red meat consumption at either level of SFA. Conclusion: Diets high in both SFA and red or white meat protein have adverse effects on IR compared with either low SF or non-meat protein consumption. Disclosure M.D.Gadgil: None. R.M.Krauss: None. Funding National Institute of Diabetes and Digestive and Kidney Diseases (R03DK132307); National Heart, Lung, and Blood Institute (R01HL106003); National Center for Advancing Translational Sciences; San Francisco Clinical and Translational Science Institute (UL1TR000004)

619-P: An Isocaloric High Saturated Fat Diet Increases Endogenous Cholesterol Production Which Is Reversed by a Protein-Enriched Diet in Normal-Weight Humans

Lathosterol is a marker of endogenous cholesterol synthesis whereas plant sterols (e. g. campesterol) reflect cholesterol absorption. Obesity and type 2 diabetes mellitus are associated with increased endogenous cholesterol production and decreased cholesterol absorption. Only few studies evaluated cholesterol homeostasis under isocaloric nutritional conditions. This study investigated endogenous cholesterol production in healthy humans after consumption of isocaloric diets enriched with carbohydrates (KH) or saturated fat (HF) or protein (HP). 24 normal weight participants (women and men, age 18 - 70) were investigated for 18 weeks. An isocaloric diet rich in carbohydrates (55% carbohydrates, 30% fat, 15% protein, KH) was applied followed by an isocaloric diet rich in saturated fat (40% carbohydrates, 45% fat, 15% protein, HF) and finally followed by an isocaloric diet enriched with proteins (45% carbohydrates, 30% fat, 25% protein, HP); each for 6 weeks. Body weight (BW), serum total and LDL cholesterol and serum lathosterol and campesterol levels were analyzed after the KH period, after one week (HF1) and 6 weeks (HF6) of the HF and after the HP period. BW did not change during the study. Serum total and LDL cholesterol increased from 4.38±0.2 and 2.74±0.2 mmol/L, respectively at KH to 4.82±0.2 and 2.97±0.2 mmol/L, respectively at HF6 (both P<0.01) and were decreased back to KH levels at HP. Serum lathosterol levels increased 1.26-fold and 1.16-fold, respectively at HF1 and HF6 (P<0.05 compared to LF), however decreased by 10.1% at HP (compared to KH levels, P<0.05). Serum campesterol levels moderately decreased at HF1 and HF6 and were restored to KH levels at HP (P<0.01 compared to HF6). These data show that composition of macronutrients are responsible for diet induced elevation of serum cholesterol levels due to an increased endogenous cholesterol production in normal weight humans regardless of the energy content of the diet. Disclosure M.Kruse: None. S.Matysik: None. D.Hoffmann: None. T.Frahnow: None. A.F.Pfeiffer: Advisory Panel; Abbott Diabetes, Speaker's Bureau; Novo Nordisk, Sanofi-Aventis Deutschland GmbH. Funding German Federal Ministry of Education and Research (0315424)

Associations of Dietary Intakes of Total and Specific Types of Fat with Blood Lipid Levels in the Filipino Women's Diet and Health Study (FiLWHEL).

Limited evidence exists on the association between dietary fat intake and lipid profiles in Southeast Asian populations. We aimed to examine the cross-sectional associations of dietary intake of total and specific types of fat with dyslipidemia in Filipino immigrant women in Korea. We included 406 Filipino women married to Korean in the Filipino Women's Diet and Health Study (FiLWHEL). Dietary fat intake was assessed using 24-hour recalls. Impaired blood lipid profiles were defined as high total cholesterol (TC) (≥200 mg/dL), high triglyceride (TG) (≥150 mg/dL), high LDL Cholesterol (LDL-C) (≥ 130 mg/dL), or low HDL cholesterol (HDL-C) (<50 mg/dL). The genomic DNA samples were genotyped using DNA chip. The odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using multivariate logistic regression. Substituting carbohydrates with dietary saturated fat (SFA) intake was associated with increased prevalence of dyslipidemia; ORs (95% CIs) for subsequent tertiles compared to the first tertile were 2.28 (1.19-4.35), and 2.88 (1.29-6.39) (P for trend = 0.02). When we examined individual markers, ORs (95% CIs, P for trend) comparing the third to the first tertile were 3.62 (1.53-8.55, 0.01) for high TC, 1.46 (0.42-5.10, 0.72) for high TG, 4.00 (1.48-10.79, 0.02) for high LDL-C, and 0.69 (0.30-1.59, 0.36) for low HDL-C. When we examined the interaction by LDL-C-related polymorphisms, the association with dyslipidemia was more pronounced among participants with CC alleles than among those with T alleles of rs6102059 (P for interaction = 0.01). High dietary SFA intake was significantly associated with a high prevalence of dyslipidemia in Filipino women in Korea. Further prospective cohort studies are warranted to determine risk factors for CVD in Southeast Asian populations.

Unsaturated or saturated dietary fat-mediated steatosis impairs hepatic regeneration following partial hepatectomy in mice.

Partial hepatectomy is a preferred treatment option for many patients with hepatocellular carcinoma however, pre-existing pathological abnormalities originating from hepatic steatosis can alter the decision to perform surgery or postoperative outcomes as a consequence of the impact steatosis has on liver regeneration. The aim of this study was to investigate the role of a saturated or unsaturated high fat diet-mediated steatosis on liver regeneration following partial hepatectomy. Mice were fed a low-fat control diet (CD, 13% fat), lard-based unsaturated (LD, 60% fat) or milk-based saturated high fat diet (MD, 60% fat) for 16 weeks at which time partial hepatectomy (approx. 70% resection) was performed. At days-2 and 7 post hepatectomy, one hour prior to euthanization, mice were injected with 5-bromo-2'-deoxyuridine in order to monitor hepatic regeneration. Serum was collected and assessed for levels of ALT and AST. Resected and regenerated liver tissue were examined for inflammation-indicative markers employing RT-PCR, Western blots, and histological methods. Mice fed LD or MD exhibited higher NAFLD scores, increased expression of inflammatory cytokines, neutrophil infiltration, macrophage accumulation, increased apoptosis, and elevated levels of serum ALT and AST activities, a decrease in the number of BrdU-incorporated-hepatocytes in the regenerated livers compared to the mice fed CD. Mice fed MD showed significantly lower percent of BrdU-incorporated hepatocytes and a higher trend of inflammation compared to the mice fed LD. A diet rich in saturated or unsaturated fat results in NASH with decreased hepatic regeneration however unsaturated fat diet cause lower inflammation and higher regeneration than the saturated fat diet following partial hepatectomy in mice.

Abstract 458: A Study Of Short-term Low-saturated Fat Versus High-saturated Fat Diet In Atherothrombosis Risk Factors In Subjects With Hypertriglyceridemia

Introduction: Dietary fat and composition may impact the risk of atherosclerotic cardiovascular disease (ASCVD) in subjects with hypertriglyceridemia (HTG). Hypothesis: We hypothesized that a low-saturated fat diet (LSFD), in contrast to a high-saturated fat diet (HSFD), improves blood lipid levels and reduces atherothrombosis risk factors in subjects with HTG. Method: Subjects with HTG and metabolic syndrome (n=19) were randomly placed on an LSFD (~25% of calories from fat, 5% from saturated fat) or an HSFD (~52% of calories from fat, 25% from saturated fat) for 4 days (day 1-4) and a breakfast on day 5 and then switched to the other diet after a 4- to 6-week washout period. Blood was collected on day 1 fasting before the start of the diet and on day 5 fasting and at 4 and 6 hours after breakfast. Lipid profiles and flow cytometry to measure monocyte intracellular lipid accumulation, monocyte expression of tissue factor (TF), and monocyte-platelet aggregates (MPAs) were performed. Results: On day 5, LSFD, compared to HSFD, induced lower plasma levels of postprandial total triglyceride and LDL-triglyceride and fasting and postprandial total cholesterol, non-HDL-cholesterol, LDL-cholesterol, and small dense LDL-cholesterol. Classical and intermediate monocytes with LSFD, in contrast to HSFD, exhibited reduced intracellular lipid accumulation indicated by decreases in cellular granularity and nile red staining examined by flow cytometry. LSFD vs. HSFD also reduced classical monocyte uptake of oxidized LDL ex vivo at 4 hours postprandially on day 5. Surface level of TF was higher on classical and intermediate monocytes than on nonclassical monocytes assessed by mean fluorescence intensity. Classical and intermediate monocytes, compared to nonclassical monocytes, were also more prone to form aggregates with platelets. However, there was no significant difference between LSFD and HSFD in TF levels on any monocyte subsets and in MPAs of any monocyte subsets at any time points recorded. Conclusion: In subjects with HTG and metabolic syndrome, short-term LSFD, in contrast to HSFD, reduced monocyte lipid accumulation and oxidized LDL uptake but did not induce significant differences in monocyte surface levels of TF and MPA formation.

Dietary Effects on Monocyte Phenotypes in Subjects With Hypertriglyceridemia and Metabolic Syndrome

In patients with hypertriglyceridemia, a short-term low-saturated fat vs high-saturated fat diet induced lowerplasma lipids and improved monocyte phenotypes. These findings highlight the role of diet fat content andcomposition for monocyte phenotypes and possibly cardiovascular disease risk in these patients. (EffectsofDietary Interventions on Monocytes in Metabolic Syndrome; NCT03591588).

Proanthocyanidins: Impact on Gut Microbiota and Intestinal Action Mechanisms in the Prevention and Treatment of Metabolic Syndrome.

The metabolic syndrome (MS) is a cluster of risk factors, such as central obesity, hyperglycemia, dyslipidemia, and arterial hypertension, which increase the probability of causing premature mortality. The consumption of high-fat diets (HFD), normally referred to high-saturated fat diets, is a major driver of the rising incidence of MS. In fact, the altered interplay between HFD, microbiome, and the intestinal barrier is being considered as a possible origin of MS. Consumption of proanthocyanidins (PAs) has a beneficial effect against the metabolic disturbances in MS. However, there are no conclusive results in the literature about the efficacy of PAs in improving MS. This review allows a comprehensive validation of the diverse effects of the PAs on the intestinal dysfunction in HFD-induced MS, differentiating between preventive and therapeutic actions. Special emphasis is placed on the impact of PAs on the gut microbiota, providing a system to facilitate comparison between the studies. PAs can modulate the microbiome toward a healthy profile and strength barrier integrity. Nevertheless, to date, published clinical trials to verify preclinical findings are scarce. Finally, the preventive consumption of PAs in MS-associated dysbiosis and intestinal dysfunction induced by HFD seems more successful than the treatment strategy.

Healthy lifestyles and wellbeing reduce neuroinflammation and prevent neurodegenerative and psychiatric disorders.

Since the mid-20th century, Western societies have considered productivity and economic outcomes are more important than focusing on people's health and wellbeing. This focus has created lifestyles with high stress levels, associated with overconsumption of unhealthy foods and little exercise, which negatively affect people's lives, and subsequently lead to the development of pathologies, including neurodegenerative and psychiatric disorders. Prioritizing a healthy lifestyle to maintain wellbeing may slow the onset or reduce the severity of pathologies. It is a win-win for everyone; for societies and for individuals. A balanced lifestyle is increasingly being adopted globally, with many doctors encouraging meditation and prescribing non-pharmaceutical interventions to treat depression. In psychiatric and neurodegenerative disorders, the inflammatory response system of the brain (neuroinflammation) is activated. Many risks factors are now known to be linked to neuroinflammation such as stress, pollution, and a high saturated and trans fat diet. On the other hand, many studies have linked healthy habits and anti-inflammatory products with lower levels of neuroinflammation and a reduced risk of neurodegenerative and psychiatric disorders. Sharing risk and protective factors is critical so that individuals can make informed choices that promote positive aging throughout their lifespan. Most strategies to manage neurodegenerative diseases are palliative because neurodegeneration has been progressing silently for decades before symptoms appear. Here, we focus on preventing neurodegenerative diseases by adopting an integrated "healthy" lifestyle approach. This review summarizes the role of neuroinflammation on risk and protective factors of neurodegenerative and psychiatric disorders.