Janus kinase-signal transducer and activator of transcription signaling pathway in the ocular cells of rat fetuses exposed to maternal saturated fat ingestion.

OBJECTIVE: The aim of this study was to analyze possible alterations (morphological and inflammatory) in the ocular cells of fetuses from mothers with insulin resistance exposed to saturated fatty acids through the period of pregnancy. METHODS: Wistar female rats were induced to develop insulin resistance before pregnancy. Fetuses' skulls were collected on the 20th day of intrauterine life. The rats were separated on the first day of management into two groups according to the diet applied: control group (C): diet containing soybean oil as a source of fat; and saturated fatty acid group (S): diet containing butter as a source of fat. RESULTS: Histological and immunohistochemical analyses have been conducted. The immunohistochemical analyses of interleukin 6, suppressor of cytokine signaling, 3 and signal transducer and activator of transcription 3 did not demonstrate alterations in the expression of proteins in the fetuses of mothers fed with a saturated fatty diet. Moreover, no histopathological changes were noticed between groups. CONCLUSION: The saturated fatty diet does not induce tissue changes or activate the Janus kinase/signal transducer and activator of transcription signaling pathway during eye development in the fetuses of mothers with insulin resistance.

The effects of paternal dietary fat versus sugar on offspring body composition and anxiety-related behavior.

Increasing evidence suggests that the pre-conception parental environment has long-term consequences for offspring health and disease susceptibility. Though much of the work in this field concentrates on maternal influences, there is growing understanding that fathers also play a significant role in affecting offspring phenotypes. In this study, we investigate effects of altering the proportion of dietary fats and carbohydrates on paternal and offspring body composition and anxiety-related behavior in C57Bl/6-JArc mice. We show that in an isocaloric context, greater dietary fat increased body fat and reduced anxiety-like behavior of studs, whereas increased dietary sucrose had no significant effect. These dietary effects were not reflected in offspring traits, rather, we found sex-specific effects that differed between offspring body composition and behavioral traits. This finding is consistent with past paternal effect studies, where transgenerational effects have been shown to be more prominent in one sex over the other. Here, male offspring of fathers fed high-fat diets were heavier at 10 weeks of age due to increased lean body mass, whereas paternal diet had no significant effect on female offspring body fat or lean mass. In contrast, paternal dietary sugar appeared to have the strongest effects on male offspring behavior, with male offspring of high-sucrose fathers spending less time in the closed arms of the elevated plus maze. Both high-fat and high-sugar paternal diets were found to reduce anxiety-like behavior of female offspring, although this effect was only evident when offspring were fed a control diet. This study provides new understanding of the ways in which diet can shape the behavior of fathers and their offspring and contribute to the development of dietary guidelines to improve obesity and mental health conditions, such as anxiety.

Monounsaturated fat-rich diet reduces body adiposity in women with obesity, but does not influence energy expenditure and substrate oxidation: a parallel randomized controlled clinical trial.

BACKGROUND: Obesity is an important and growing health problem whose treatment involves dietary changes. In this context, studying the role of macronutrients in weight loss is required in order to understand which strategies may be applied for weight loss. We aimed to evaluate the effects of diets rich in polyunsaturated (PUFAs) and monounsaturated fatty acids (MUFAs) on resting energy expenditure (REE), substrate oxidation, and weight loss in women with obesity. METHODS: Randomized, controlled, single blind, parallel-group clinical trial was conducted for 60 days. Participants (n = 32) were divided into three groups: G1= normocaloric PUFAs-rich diet (12% of total energy expenditure (TEE), 10% of n-6 and up to 2% of n-3); G2= normocaloric MUFAs-rich diet (15-20% TEE); and G3= maintenance of the usual diet. Anthropometric and metabolic variables (REE and substrate oxidation by indirect calorimetry) were evaluated. RESULTS: G2 decreased body weight (-1.92 ± 1.99 kg, P = 0.02), body mass index (BMI) (-0.69 ± 0.70 kg/m2; P = 0.02), waist circumference (WC) (-1.91 ± 1.82 cm; P = 0.02), and body fat (-1.14 ± 1.53 kg; P = 0.04). CONCLUSION: MUFAs-rich diet reduces body weight, BMI, body fat, and WC. CLINICAL TRIALS: NCT02656940. CLINICAL TRIAL REGISTRATION: Clinical Trials: NCT02656940.

Dietary-fat supplementation alleviates cold temperature-induced metabolic dysbiosis and barrier impairment by remodeling gut microbiota.

As important components of the mammalian diet and tissues, fats are involved in a variety of biological processes in addition to providing energy. In general, the increase in basal metabolism and health risks under cold temperature conditions causes the host to need more energy to maintain body temperature and normal biological processes. The intestine and its microbiota are key components in orchestrating host metabolic homeostasis and immunity, and respond rapidly to changing environmental conditions. However, the role of dietary-fat supplementation in regulating host homeostasis of metabolism and barrier functions through gut microbiota at cold temperatures is incompletely understood. Our results showed that dietary-fat supplementation alleviated the negative effects of cold temperatures on the alpha-diversity of both ileal and colonic microbiota. Cold temperatures altered the ileal and colonic microbiota of pigs, and the extent of changes was more pronounced in the colonic microbiota. Translocation of the gut microbiota was restored after supplementation with a high-fat diet. In addition, cold temperatures exacerbated ileal mucosal damage and inflammation, and disrupted barrier function, which may be associated with decreased concentrations of butyrate and isobutyrate. Cold temperature-induced metabolic dysbiosis was manifested by altered hormone levels and upregulation of expression of multiple metabolites involved in metabolism (lipids, amino acids and minerals) and the immune response. Supplementation with a high-fat diet restored metabolic homeostasis and barrier function by improving gut-microbiota composition and increasing SCFAs concentrations in pigs. In conclusion, cold temperatures induced severe translocation of microbiota and barrier damage. These actions increased the risk of metabolic imbalance. Dietary-fat supplementation alleviated the adverse effects of cold temperatures on host metabolism by remodeling the gut microbiota.

Fructose corn syrup induces inflammatory injury and obesity by altering gut microbiota and gut microbiota-related arachidonic acid metabolism.

Excessive fructose corn syrup (FCS) intake brings a series of health problems. The aim of the present study was to explore the mechanism of FCS-induced metabolic disorders from the perspective of gut microbiota. Mice were fed for 16 weeks with normal or 30% FCS drinking water. Compared to the control group, FCS caused significantly higher fat deposition, hepatic steatosis, liver and intestinal inflammatory damages (P<.05). FCS increased the abundance of Muribaculaceae in vivo and in vitro, which was positively correlated with the indices of metabolic disorders (P<.05). In vivo and in vitro data indicated that FCS enhanced the microbial function involved in pentose phosphate pathway and arachidonic acid metabolism, metabolomics further demonstrated that FCS led to an increase in prostaglandins (the catabolites of arachidonic acid) (P<.05). Our study confirmed that FCS can directly promote gut microbiota to synthesize inflammatory factor prostaglandins, which provides new insights and directions for the treatment of FCS-induced metabolic disorders and inflammation.

Effects of dietary fat, nitrate, and 3-nitrooxypropanol and their combinations on methane emission, feed intake, and milk production in dairy cows.

The objective of the present study was to investigate the effect of individual and combined use of dietary fat, nitrate, and 3-nitrooxypropanol (3-NOP) on dairy cows' enteric methane (CH4) emission and production performance. Twenty-four primiparous and 24 multiparous Danish Holstein cows (111 ± 44.6 d in milk; mean ± standard deviation) were included in an incomplete 8 × 8 Latin square design with six 21-d periods. Dietary treatments were organized in a 2 × 2 × 2 factorial arrangement aiming for 2 levels of FAT (30 or 63 g of crude fat/kg of dry matter [DM]; LF or HF, respectively), 2 levels of NITRATE (0 or 10 g of nitrate/kg of DM; UREA or NIT, respectively), and 2 levels of 3-NOP (0 or 80 mg/kg DM; BLANK or NOP, respectively). Treatments were included in ad libitum-fed partial mixed rations in bins that automatically measured feed intake and eating behavior. Additional concentrate was offered as bait in GreenFeed units used for measurement of gas emission. For total DM intake (DMI), a FAT × NITRATE interaction showed that DMI, across parities and levels of 3-NOP, was unaffected by separate fat supplementation, but reduced by nitrate with 4.6% and synergistically decreased (significant 2-way interaction) with 13.0% when fat and nitrate were combined. Additionally, 3-NOP decreased DMI by 13.4% and the combination of 3-NOP with fat and nitrate decreased DMI in an additive way (no significant 3-way interaction). The decreasing effects on DMI were more pronounced in multiparous cows than in primiparous cows. For treatments with largest reductions in DMI, eating behavior was altered toward more frequent, but smaller meals, a slower eating rate and increased attempts to visit unassigned feed bins. Energy-corrected milk (ECM) yield increased by 6.3% with fat supplementation, whereas ECM yield did not differ among diets including nitrate (FAT × NITRATE interaction). Cows supplemented with 3-NOP had 9.0% lower ECM yield than cows fed no 3-NOP. Based on three 2-way interactions including FAT, NITRATE, and 3-NOP, the combined use of the additives resulted in antagonistic effects on CH4 reduction. A 6% to 7% reduction in CH4 yield (CH4/kg of DMI) could be ascribed to the effect of fat, a 12% to 13% reduction could be ascribed to the effect of nitrate and an 18% to 23% reduction could be ascribed to the effect of 3-NOP. Hence, no combinations of additives resulted in CH4 yield-reductions that were greater than what was obtained by separate supplementation of the most potent additive within the combination. The CH4 yield reduction potential of additives was similar between parities. Increased apparent total-tract digestibility of organic matter (OM) in cows fed combinations including nitrate or 3-NOP was a result of a NITRATE × 3-NOP interaction. Apparent total-tract digestibility of OM was also increased by fat supplementation. These increases reflected observed decreases in DMI. In conclusion, combined use of fat, nitrate, and 3-NOP in all combinations did not result in CH4 reductions that were greater than separate supplementation of the most potent additive within the combination (3-NOP > nitrate > fat). Additionally, separate supplementation of some additives and combined use of all additives reduced DMI.

Fat from Hermetia illucens Alters the Cecal Gut Microbiome and Lowers Hepatic Triglyceride Concentration in Comparison to Palm Oil in Obese Zucker Rats.

BACKGROUND: Palm oil (PO) is the most widely utilized plant oil for food production. Owing to the great ecologic problems associated with PO production, sustainably produced fats, such as insect fat, might be a suitable alternative. OBJECTIVES: The hypothesis was tested that fat from Hermetia illucens larvae (HF) compared with PO and soybean oil (SO) has no adverse effects on hepatic lipid metabolism, plasma metabolome, and cecal microbiome in obese Zucker rats. METHODS: Thirty male obese Zucker rats were randomly assigned to 3 groups (SO, PO, HF; n = 10 rats/group) and fed 3 different semisynthetic diets containing either SO, PO, or HF as the main fat source for 4 wk. The effects were evaluated by measurement of liver and plasma lipid concentrations, liver transcriptomics, targeted plasma metabolomics, and cecal microbiomics. RESULTS: Supplementation of HF reduced hepatic triglyceride concentration and messenger ribonucleic acid concentrations of selected genes involved in fatty acid and triglyceride synthesis in comparison to PO (P < 0.05). Pairwise comparison of the Simpson index and Jaccard index showed a higher cecal microbial α- and ß-diversity in rats fed the HF diet than in rats fed the PO diet (P = 0.015 and P = 0.027), but no difference between rats fed the diets with SO or PO. Taxonomic analysis of the cecal microbial community revealed a lower abundance of Clostridium_sensu_stricto_1 and a higher abundance of Blautia, Mucispirillum, Anaerotruncus, Harryflintia, and Peptococcus in rats supplemented with HF than in rats supplemented with PO (P < 0.05). CONCLUSIONS: HF, compared with PO, has liver lipid-lowering effects in obese Zucker rats, which may be caused by a shift in the gut microbial community. Thus, HF might serve as a sustainably produced fat alternative to PO for food production.

Impact of various high fat diets on gene expression and the microbiome across the mouse intestines.

High fat diets (HFDs) have been linked to several diseases including obesity, diabetes, fatty liver, inflammatory bowel disease (IBD) and colon cancer. In this study, we examined the impact on intestinal gene expression of three isocaloric HFDs that differed only in their fatty acid composition-coconut oil (saturated fats), conventional soybean oil (polyunsaturated fats) and a genetically modified soybean oil (monounsaturated fats). Four functionally distinct segments of the mouse intestinal tract were analyzed using RNA-seq-duodenum, jejunum, terminal ileum and proximal colon. We found considerable dysregulation of genes in multiple tissues with the different diets, including those encoding nuclear receptors and genes involved in xenobiotic and drug metabolism, epithelial barrier function, IBD and colon cancer as well as genes associated with the microbiome and COVID-19. Network analysis shows that genes involved in metabolism tend to be upregulated by the HFDs while genes related to the immune system are downregulated; neurotransmitter signaling was also dysregulated by the HFDs. Genomic sequencing also revealed a microbiome altered by the HFDs. This study highlights the potential impact of different HFDs on gut health with implications for the organism as a whole and will serve as a reference for gene expression along the length of the intestines.

Reducing Dietary Polyunsaturated to Saturated Fatty Acids Ratio Improves Lipid and Glucose Metabolism in Obese Zucker Rats.

We investigated the influence of varying dietary polyunsaturated fatty acid (PUFA)/saturated fatty acids (SFA) ratios on insulin resistance (IR), fatty acid metabolism, N-acylethanolamine (NAE) bioactive metabolite levels, and mitochondrial function in lean and obese Zucker rats in a model designed to study obesity and IR from overnutrition. We provided diets with 7% fat (w/w), with either a low PUFA/SFA ratio of 0.48, predominantly comprising palmitic acid (PA), (diet-PA), or the standard AIN-93G diet with a high PUFA/SFA ratio of 3.66 (control, diet-C) over eight weeks. In obese rats on diet-PA versus diet-C, there were reductions in plasma triglycerides, cholesterol, glucose, insulin concentrations and improved muscle mitochondrial function, inflammatory markers and increased muscle N-oleoylethanolamine (OEA), a bioactive lipid that modulates lipid metabolism and metabolic flexibility. Elevated palmitic acid levels were found exclusively in obese rats, regardless of their diet, implying an endogenous production through de novo lipogenesis rather than from a dietary origin. In conclusion, a reduced dietary PUFA/SFA ratio positively influenced glucose and lipid metabolism without affecting long-term PA tissue concentrations. This likely occurs due to an increase in OEA biosynthesis, improving metabolic flexibility in obese rats. Our results hint at a pivotal role for balanced dietary PA in countering the effects of overnutrition-induced obesity.

Integration of hepatic lipidomics and transcriptomics reveals the effect of butter-derived ruminant trans fatty acids on lipid metabolism in C57BL/6J mice.

Dysregulation of lipid metabolism results in metabolism-related diseases. Our previous research indicated that 1.3% E and 4% E ruminant trans fatty acids (R-TFA) caused dyslipidemia and promoted atherosclerotic plaques in ApoE-/- mice, presenting detrimental effects. However, the effect of R-TFA on the lipid metabolism of normal mice remains unclear. Therefore, our current research aims to explore the effects of butter-derived R-TFAs on the lipid metabolism of C57BL/6J mice through the integration of lipidomics and transcriptomics. As a result, we found that 1.3% E butter-derived R-TFA promoted dyslipidemia and impaired hepatic function in C57BL/6J mice fed a high-fat diet, which was associated with an increase in DG (18:1/22:5), TG (18:1/18:2/22:4) and FA (24:5) as determined through lipidomics analysis, but had a less significant effect on C57BL/6J mice fed a low-fat diet. Through a combination analysis and verification of gene expression, we found that the arachidonic acid pathway might be involved in the disruption of lipid metabolism by butter-derived R-TFA. In addition, butter-derived R-TFA up-regulated the expression of unigene thromboxane-A synthase 1 (Tbxas1), arachidonate lipoxygenase 3 (Aloxe3), acyl-coenzyme A thioesterase 2 (Acot2), epoxide hydrolase 2 (Ephx2) and carbonyl reductase 3 (Cbr3) in C57BL/6J mice fed a high-fat diet. Herein, our research provides a new perspective for exploring the effects of butter-derived R-TFA on lipid metabolism and speculates on the possible mechanism of lipid metabolism disorder induced by butter-derived R-TFA in C57BL/6J mice fed a high-fat diet.

Systematic Review and Quantitative Data Synthesis of Peripheral Blood Mononuclear Cell Transcriptomics Reveals Consensus Gene Expression Changes in Response to a High Fat Meal.

SCOPE: Metabolic flexibility is essential for a healthy response to a high fat meal, and is assessed by measuring postprandial changes in blood markers including peripheral blood mononuclear cells (PBMCs; lymphocytes and monocytes). However, there is no clear consensus on postprandial gene expression and protein changes in these cells. METHOD AND RESULTS: The study systematically reviews the literature reporting transcriptional and proteomic changes in PBMCs after consumption of a high fat meal. After re-analysis of the raw data to ensure equivalence between studies, ≈85 genes are significantly changed (defined as in the same direction in ≥3 studies) with about half involved in four processes: inflammation/oxidative stress, GTP metabolism, apoptosis, and lipid localization/transport. For meals consisting predominantly of unsaturated fatty acids (UFA), notable additional processes are phosphorylation and glucocorticoid response. For saturated fatty acids (SFA), genes related to migration/angiogenesis and platelet aggregation are also changed. CONCLUSION: Despite differences in study design, common gene changes are identified in PBMCs following a high fat meal. These common genes and processes will facilitate definition of the postprandial transcriptome as part of the overall postcibalome, linking all molecules and processes that change in the blood after a meal.

Effect of Isoenergetic Substitution of Cheese with Other Dairy Products on Blood Lipid Markers in the Fasted and Postprandial State: An Updated and Extended Systematic Review and Meta-Analysis of Randomized Controlled Trials in Adults.

Consumption of fat as part of a cheese matrix may differentially affect blood lipid responses when compared with other dairy foods. This systematic review was conducted to compare the impact of consuming equal amounts of fat from cheese and other dairy products on blood lipid markers in the fasted and postprandial state. Searches of PubMed (Medline), Cochrane Central and Embase databases were conducted up to mid-June 2022. Eligible human randomized controlled trials (RCTs) investigated the effect of isoenergetic substitution of hard or semi-hard cheese with other dairy products on blood lipid markers. Risk of bias (RoB) was assessed using the Cochrane RoB 2.0 tool. Random-effects meta-analyses assessed the effect of ≥2 similar dietary replacements on the same blood lipid marker. Of 1491 identified citations, 10 articles were included (RoB: all some concerns). Pooled analyses of 7 RCTs showed a reduction in fasting total cholesterol, LDL-C and HDL-C concentrations after ≥14 d mean daily intake of 135 g cheese (weighted mean difference [WMD]: -0.24 mmol/L; 95% confidence interval (CI): -0.34, -0.15; I2 = 59.8%, WMD: -0.19 mmol/L; 95% CI: -0.27, -0.12; I2 = 42.8%, and WMD: -0.04 mmol/L; 95% CI: -0.08, -0.00; I2 = 58.6%, respectively) relative to ∼52 g/d butter. We found no evidence of a benefit from replacing cheese for ≥14 d with milk on fasting blood lipid markers (n = 2). Limited postprandial RCTs, described in narrative syntheses, suggested that cheese-rich meals may induce differential fed-state lipid responses compared with some other dairy matrix structures, but not butter (n ≤ 2). In conclusion, these findings indicate that dairy fat consumed in the form of cheese has a differential effect on blood lipid responses relative to some other dairy food structures. However, owing to considerable heterogeneity and limited studies, further confirmation from RCTs is warranted. TRIAL REGISTRATION NUMBER: This systematic review protocol was registered at https://www.crd.york.ac.uk/PROSPERO/ as CRD42022299748.

Effect of exogenous bile salts supplementation on the performance and hepatic lipid metabolism of aged laying hens.

Bile acids (BA), a series of hydroxylated steroids secreted by the liver, are involved in the digestion and absorption of dietary fats. In the present study, the effect of exogenous BAs on the performance and liver lipid metabolism of laying hens was investigated. Three hundred and sixty 50-wk-old Hy-line Brown hens were randomly allocated into three groups and subjected to one of the following treatments: fed with the basal diet (control, Con), the basal diet supplemented with 0.1 g/kg (0.1 g/kg BAs), or 0.2 g/kg (0.2 g/kg BAs) porcine BAs. Laying performance, egg quality, and blood parameters were measured during the 8-wk experimental period. The expression of genes related to hepatic lipid metabolism was determined at the end of experiment. The results showed that BAs treatments had no influence (P > 0.05) on laying rate, egg weight, and feed efficiency. BAs treatment, however, significantly decreased mortality of hens (P = 0.006). BAs treatment showed a transient negative influence on eggshell quality at week 4 but not at week 8. The yolk color on week 8 was increased by BAs treatments (P < 0.0001) compared to control. The duodenum index showed a tendency to be increased (P = 0.053) and jejunum index were increased (P = 0.007) by BAs treatment. Compared to control, BAs treatments decreased lipid droplet content (P < 0.0001) and TG content (P = 0.002) of liver. Fatty acid synthase activity was also decreased as an effect of BAs dietary supplementation. Compared to the control group, 0.1 g/kg BAs treatment increased (P < 0.05) the mRNA expression of genes Farnesoid X receptor (FXR) (P = 0.042), cytochrome P450 family 7 subfamily A member 1 (CYP7A1) (P = 0.002), and cytochrome P450 family 8 subfamily B member 1 (CYP8B1) (P = 0.017), fatty acid synthase (FAS) (P = 0.020), acetyl-CoA carboxylase (ACC) (P = 0.032), sterol regulatory element binding protein-1c (SREBP-1c) (P = 0.037), proliferator-activated receptor gamma (PPARγ) (P = 0.002), apolipoprotein B (APO-B) (P = 0.020), and very low density lipoprotein receptor (VLDLR) (P = 0.024). In conclusion, the addition of exogenous BAs reduces lipid accumulation in liver. BA supplementation reduces the mortality of hens and improves egg yolk color, with no unfavorable effect on laying performance. The result suggests that suppressed FAS activity is involved in the reduced hepatic lipid accumulation by BAs treatment.

Fatty liver hemorrhagic syndrome is one of the most common diseases in laying hens and is a metabolic disease characterized by disorders of lipid metabolism in the liver, manifested by fatty liver degeneration and varying degrees of hemorrhage, which often occurs in caged hens in good condition and with high egg production rates. Bile acids (BA), a group of hydroxylated steroids synthesized from cholesterol in the liver, play an important role in lipid metabolism. This study aimed to examine the effects of dietary addition of different levels of BAs on the production performance and liver fat metabolism of 50-wk-old Hy-line Brown hens. The result indicates that the addition of exogenous BAs reduces lipid accumulation in liver. BAs supplementation reduces the mortality of hens and improves egg yolk color, with no other unfavorable side effects on laying performance. The results of the present study suggest that suppressed fatty acid synthase activity is involved in the reduced hepatic lipid accumulation as an effect of BAs dietary supplementation.

Post-nursing early life macronutrient balance promotes persistent and malleable biometric and metabolic traits in mice.

It is known that dietary factors within the gestational and nursing period affect early life and stably affect later life traits in animals. However, there is very little understanding of whether dietary factors within the early life period from post-nursing to adulthood affect traits in adulthood. To address this, we conducted studies on male C57Bl/6J mice fed from 3 weeks (immediately post-nursing) until 12 weeks (full maturity) using nine different diets varying in all three major macronutrients to parse out the effects of individual macronutrients. Early life macronutrient balance affected body composition and glucose homeostasis in early adulthood, with dietary protein and fat showing major effects. Despite this, mice showed rapid reversal of the effects on body composition and glucose homeostasis of early life diet feeding, upon standard diet feeding in adulthood. However, some traits were persistent, with early life low dietary protein levels stably affecting lean and muscle mass, and early life dietary fat levels stably affecting serum and liver triglyceride levels. In summary, macronutrient balance in the post-nursing early life period does not stably affect adiposity or glucose homeostasis but does impact muscle mass and lipid homeostasis in adulthood, with prominent effects of both protein and fat levels. KEY POINTS: Early life dietary low protein and high fat levels lowered and heightened body mass, respectively. These effects did not substantially persist into adulthood with rapid catch-up growth on a normal diet. Early life protein (negative) and fat (positive) levels affected fat mass. Early life low protein levels negatively affected lean mass. Low protein effects on lower lean and muscle mass persisted into adulthood. Early life macronutrient balance effects did not affect later life glucose homeostasis but early life high fat level affected later life dyslipidaemia. Effects of dietary carbohydrate levels in early and later life were minor.

Beyond ingredients: Supramolecular structure of lipid droplets in infant formula affects metabolic and brain function in mouse models.

Human milk beneficially affects infant growth and brain development. The supramolecular structure of lipid globules in human milk i.e., large lipid globules covered by the milk fat globule membrane, is believed to contribute to this effect, in addition to the supply of functional ingredients. Three preclinical (mouse) experiments were performed to study the effects of infant formula mimicking the supramolecular structure of human milk lipid globules on brain and metabolic health outcomes. From postnatal day 16 to 42, mouse offspring were exposed to a diet containing infant formula with large, phospholipid-coated lipid droplets (structure, STR) or infant formula with the same ingredients but lacking the unique structural properties as observed in human milk (ingredient, ING). Subsequently, in Study 1, the fatty acid composition in liver and brain membranes was measured, and expression of hippocampal molecular markers were analyzed. In Study 2 and 3 adult (Western-style diet-induced) body fat accumulation and cognitive function were evaluated. Animals exposed to STR compared to ING showed improved omega-3 fatty acid accumulation in liver and brain, and higher expression of brain myelin-associated glycoprotein. Early exposure to STR reduced fat mass accumulation in adulthood; the effect was more pronounced in animals exposed to a Western-style diet. Additionally, mice exposed to STR demonstrated better memory performance later in life. In conclusion, early life exposure to infant formula containing large, phospholipid-coated lipid droplets, that are closer to the supramolecular structure of lipid globules in human milk, positively affects adult brain and metabolic health outcomes in pre-clinical animal models.

Impact of saturated compared with unsaturated dietary fat on insulin sensitivity, pancreatic ß-cell function and glucose tolerance: a systematic review and meta-analysis of randomized, controlled trials.

BACKGROUND: The impact of the dietary fat type on type 2 diabetes (T2D) remains unclear. OBJECTIVES: We aimed to evaluate the effects of replacing dietary saturated fatty acids (SFA) with mono- or poly-unsaturated fatty acids (MUFA and PUFA, respectively) on insulin sensitivity, pancreatic ß-cell function, and glucose tolerance, as surrogate endpoints for T2D. METHODS: We conducted a systematic review and meta-analysis of randomized controlled trials that replaced ≥5% of total energy intake provided by SFA with MUFA or PUFA and reported indexes of insulin sensitivity, ß-cell function, and/or glucose tolerance. We searched MEDLINE, Scopus, and the Cochrane Library (CENTRAL) up to 9 January, 2023. Eligible interventions had to be isocaloric, with no significant difference in other macronutrients. Data were synthesized using random-effects model meta-analysis. RESULTS: Of 6355 records identified, 10 parallel and 20 crossover trials with 1586 participants were included. The mean age of the participants was 42 years, 47% were male, mean body mass index (BMI; in kg/m2) was 26.8, median baseline fasting glucose was 5.13 mmol/L, and the median duration of interventions was 5 weeks. Replacing SFA with MUFA or PUFA had no significant effects on insulin sensitivity [standardized mean difference (SMD) SFA compared with MUFA: 0.01, 95% confidence interval (CI): -0.06 to 0.09, I2 = 0% and SMD SFA compared with PUFA: 0, 95% CI: -0.15 to 0.14, I2 = 0%]. Replacing SFA with MUFA did not significantly impact the ß-cell function, evaluated by the disposition index (mean difference: -12, 95% CI: -158 to 133, I2=0%). Evidence on glucose tolerance (SFA compared with MUFA or PUFA) and on ß-cell function when SFA were replaced with PUFA was scant. CONCLUSIONS: Short-term substitution of saturated with unsaturated fat does not significantly affect insulin sensitivity nor ß-cell function (the latter in the SFA compared with MUFA comparison). Future studies are needed to elucidate longer term effects of dietary fat saturation on glucose homeostasis. This trial was registered at PROSPERO as CRD42020178382.

Metabolic profiles reflect weight loss maintenance and the composition of diet after very-low-energy diet.

BACKGROUND & AIMS: Diet and weight loss affect circulating metabolome. However, metabolite profiles induced by different weight loss maintenance diets and underlying longer term weight loss maintenance remain unknown. Herein, we investigated after-weight-loss metabolic signatures of two isocaloric 24-wk weight maintenance diets differing in satiety value due to dietary fibre, protein and fat contents and identified metabolite features that associated with successful weight loss maintenance. METHODS: Non-targeted LC-MS metabolomics approach was used to analyse plasma metabolites of 79 women and men (mean age ± SD 49.7 ± 9.0 years; BMI 34.2 ± 2.5 kg/m2) participating in a weight management study. Participants underwent a 7-week very-low-energy diet (VLED) and were thereafter randomised into two groups for a 24-week weight maintenance phase. Higher satiety food (HSF) group consumed high-fibre, high-protein, and low-fat products, while lower satiety food (LSF) group consumed isocaloric low-fibre products with average protein and fat content as a part of their weight maintenance diets. Plasma metabolites were analysed before the VLED and before and after the weight maintenance phase. Metabolite features discriminating HSF and LSF groups were annotated. We also analysed metabolite features that discriminated participants who maintained ≥10% weight loss (HWM) and participants who maintained <10% weight loss (LWM) at the end of the study, irrespective of the diet. Finally, we assessed robust linear regression between metabolite features and anthropometric and food group variables. RESULTS: We annotated 126 metabolites that discriminated the HSF and LSF groups and HWM and LWM groups (p < 0.05). Compared to LSF, the HSF group had lower levels of several amino acids, e.g. glutamine, arginine, and glycine, short-, medium- and long-chain acylcarnitines (CARs), odd- and even-chain lysoglycerophospholipids, and higher levels of fatty amides. Compared to LWM, the HWM group in general showed higher levels of glycerophospholipids with a saturated long-chain and a C20:4 fatty acid tail, and unsaturated free fatty acids (FFAs). Changes in several saturated odd- and even-chain LPCs and LPEs and fatty amides were associated with the intake of many food groups, particularly grain and dairy products. Increase in several (lyso)glycerophospholipids was associated with decrease in body weight and adiposity. Increased short- and medium-chain CARs were related to decreased body fat-free mass. CONCLUSIONS: Our results show that isocaloric weight maintenance diets differing in dietary fibre, protein, and fat content affected amino acid and lipid metabolism. Increased abundances of several phospholipid species and FFAs were related with greater weight loss maintenance. Our findings indicate common and distinct metabolites for weight and dietary related variables in the context of weight reduction and weight management. The study was registered in isrctn.org with identifier 67529475.

Fatty acid composition of cholesterol esters reflects dietary fat intake after dietary interventions in a multinational population.

BACKGROUND: The effects of different dietary fatty acids (FA) on cardiovascular risk still needs clarification. Plasma lipids composition may be a biomarker of FA dietary intake. PURPOSE: To evaluate in a composite population the relationships between changes in dietary fat intake and changes in FA levels in serum cholesterol esters. METHODS: In a multinational, parallel-design, dietary intervention (KANWU study), dietary intakes (3-day food record) and FA composition of serum cholesterol esters (gas-liquid chromatography) were evaluated at baseline and after 3 months in 162 healthy individuals, randomly assigned to a diet containing a high proportion of saturated (SFA) or monounsaturated (MUFA) fat, with a second random assignment to fish oil or placebo supplements. RESULTS: Main differences in serum lipid composition after the two diets included saturated (especially myristic, C14:0, and pentadecanoic, C15:0) and monounsaturated (oleic acid, C18:1 n-9) FA. C14:0 and C15:0 were related to SFA intake, while C18:1 n-9 was associated with MUFA intake. Fish oil supplementation induced a marked increase in eicosapentaenoic (C20:5 n-3) and docosahexaenoic (C22:6 n-3) acids. After the 3-month intervention, Δ-9 desaturase activity, calculated as palmitoleic acid/palmitic acid (C16:1/C16:0) ratio, was more reduced after the MUFA (0.31±0.10 vs 0.25±0.09, p<0.0001) than SFA diet (0.31±0.09 vs 0.29±0.08, p=0.006), with a statistically significant difference between the two groups (p<0.0001). CONCLUSIONS: This study shows that serum cholesterol ester FA composition can be used during randomized controlled trials as an objective indicator of adherence to experimental diets based on saturated and monounsaturated fat modifications, as well as fish oil supplementation.

Intermittent fasting combined with exercise training reduces body mass and alleviates hypothalamic disorders induced by high-fat diet intake.

High-fat diet consumption causes hypothalamic inflammation, dysregulating the leptin pathway, which, in turn, compromises the modulation of hypothalamic neuronal activities and predisposes obesity development. Intermittent fasting (IF) and exercise training (ET) have been demonstrated as efficient interventions to modulate hypothalamic inflammation and neuronal activity. However, no studies have evaluated whether combining these interventions could induce better results in reestablishing hypothalamic homeostasis disrupted by high-fat diet intake. The 8-week-old male C57BL/6 mice were randomly assigned into 2 groups: sedentary mice fed a standard diet (CT), and sedentary mice fed a high-fat diet (HF). After 8 weeks of an HF diet, part of the HF group (now 16 weeks old) was randomly subjected to different interventions for 6 weeks: HF-IF = HF diet mice submitted to IF; HF-T = HF diet mice submitted to ET; HF-IFT = HF diet mice submitted to IF and ET. All interventions decreased the body weight gain induced by high-fat diet intake, associated with reduced calorie consumption in week 14. Only the HF-IFT group presented improved serum insulin, leptin, resistin, and Tnf-alpha levels concomitantly with decreased hypothalamic inflammation. The HF-IFT group also demonstrated increased Pomc mRNA expression associated with enhanced pSTAT3 expression in the hypothalamic arcuate and ventromedial hypothalamic nuclei. Our data indicate that the beneficial effects of the combination of IF and ET on energy homeostasis are associated with increased leptin sensitivity in the hypothalamic arcuate nucleus and ventromedial hypothalamic nucleus, which is likely due to an improvement in hypothalamic inflammatory pathways in these nuclei.

Male reproductive traits are differentially affected by dietary macronutrient balance but unrelated to adiposity.

Dietary factors influence male reproductive function in both experimental and epidemiological studies. However, there are currently no specific dietary guidelines for male preconception health. Here, we use the Nutritional Geometry framework to examine the effects of dietary macronutrient balance on reproductive traits in C57BL/6 J male mice. Dietary effects are observed in a range of morphological, testicular and spermatozoa traits, although the relative influence of protein, fat, carbohydrate, and their interactions differ depending on the trait being examined. Interestingly, dietary fat has a positive influence on sperm motility and antioxidant capacity, differing to typical high fat diet studies where calorie content is not controlled for. Moreover, body adiposity is not significantly correlated with any of the reproductive traits measured in this study. These results demonstrate the importance of macronutrient balance and calorie intake on reproductive function and support the need to develop specific, targeted, preconception dietary guidelines for males.