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1.
Food Res Int ; 186: 114317, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38729709

ABSTRACT

Lipids play a pivotal role in the nutrition of preterm infants, acting as a primary energy source. Due to their underdeveloped gastrointestinal systems, lipid malabsorption is common, leading to insufficient energy intake and slowed growth. Therefore, it is critical to explore the reasons behind the low lipid absorption rate in formulas for preterm infants. This study utilized a simulated in intro gastrointestinal digestion model to assess the differences in lipid digestion between preterm human milk and various infant formulas. Results showed that the fatty acid release rates for formulas IF3, IF5, and IF7 were 58.90 %, 56.58 %, and 66.71 %, respectively, lower than human milk's 72.31 %. The primary free fatty acids (FFA) and 2-monoacylglycerol (2-MAG) released during digestion were C14:0, C16:0, C18:0, C18:1n-9, and C18:2n-6, in both human milk and formulas. Notably, the higher release of C16:0 in formulas may disrupt fatty acid balance, impacting lipid absorption. Further investigations are necessary to elucidate lipid absorption differences, which will inform the optimization of lipid content in preterm infant formulas.


Subject(s)
Digestion , Infant Formula , Infant, Premature , Milk, Human , Milk, Human/chemistry , Milk, Human/metabolism , Humans , Infant Formula/chemistry , Infant, Newborn , Fatty Acids/analysis , Fatty Acids/metabolism , Lipids/analysis , Fatty Acids, Nonesterified/analysis , Fatty Acids, Nonesterified/metabolism , Lipid Metabolism , Gastrointestinal Tract/metabolism , Models, Biological , Monoglycerides/metabolism , Monoglycerides/analysis , Dietary Fats/metabolism , Dietary Fats/analysis
2.
Nat Commun ; 15(1): 4410, 2024 May 23.
Article in English | MEDLINE | ID: mdl-38782979

ABSTRACT

Pancreatic ß cells secrete insulin in response to glucose elevation to maintain glucose homeostasis. A complex network of inter-organ communication operates to modulate insulin secretion and regulate glucose levels after a meal. Lipids obtained from diet or generated intracellularly are known to amplify glucose-stimulated insulin secretion, however, the underlying mechanisms are not completely understood. Here, we show that a Drosophila secretory lipase, Vaha (CG8093), is synthesized in the midgut and moves to the brain where it concentrates in the insulin-producing cells in a process requiring Lipid Transfer Particle, a lipoprotein originating in the fat body. In response to dietary fat, Vaha stimulates insulin-like peptide release (ILP), and Vaha deficiency results in reduced circulatory ILP and diabetic features including hyperglycemia and hyperlipidemia. Our findings suggest Vaha functions as a diacylglycerol lipase physiologically, by being a molecular link between dietary fat and lipid amplified insulin secretion in a gut-brain axis.


Subject(s)
Brain , Drosophila Proteins , Drosophila melanogaster , Insulin Secretion , Insulin , Animals , Drosophila Proteins/metabolism , Drosophila Proteins/genetics , Brain/metabolism , Insulin/metabolism , Insulin-Secreting Cells/metabolism , Brain-Gut Axis/physiology , Lipase/metabolism , Lipase/genetics , Dietary Fats/metabolism , Glucose/metabolism , Fat Body/metabolism , Lipoprotein Lipase/metabolism , Lipoprotein Lipase/genetics , Male
3.
Cell Rep ; 43(5): 114238, 2024 May 28.
Article in English | MEDLINE | ID: mdl-38748875

ABSTRACT

Triacylglyceride (TAG) synthesis in the small intestine determines the absorption of dietary fat, but the underlying mechanisms remain to be further studied. Here, we report that the RNA-binding protein HuR (ELAVL1) promotes TAG synthesis in the small intestine. HuR associates with the 3' UTR of Dgat2 mRNA and intron 1 of Mgat2 pre-mRNA. Association of HuR with Dgat2 3' UTR stabilizes Dgat2 mRNA, while association of HuR with intron 1 of Mgat2 pre-mRNA promotes the processing of Mgat2 pre-mRNA. Intestinal epithelium-specific HuR knockout reduces the expression of DGAT2 and MGAT2, thereby reducing the dietary fat absorption through TAG synthesis and mitigating high-fat-diet (HFD)-induced non-alcoholic fatty liver disease (NAFLD) and obesity. Our findings highlight a critical role of HuR in promoting dietary fat absorption.


Subject(s)
Diet, High-Fat , ELAV-Like Protein 1 , Intestinal Absorption , Triglycerides , Triglycerides/metabolism , Triglycerides/biosynthesis , Animals , ELAV-Like Protein 1/metabolism , ELAV-Like Protein 1/genetics , Mice , Diet, High-Fat/adverse effects , Humans , Mice, Inbred C57BL , Male , Diacylglycerol O-Acyltransferase/metabolism , Diacylglycerol O-Acyltransferase/genetics , Non-alcoholic Fatty Liver Disease/metabolism , Non-alcoholic Fatty Liver Disease/pathology , Non-alcoholic Fatty Liver Disease/genetics , Obesity/metabolism , Obesity/genetics , RNA, Messenger/metabolism , RNA, Messenger/genetics , Dietary Fats/metabolism , Dietary Fats/pharmacology , Mice, Knockout , 3' Untranslated Regions/genetics , Acyltransferases
4.
Food Chem ; 450: 139353, 2024 Aug 30.
Article in English | MEDLINE | ID: mdl-38636376

ABSTRACT

Understanding neural pathways and cognitive processes involved in the transformation of dietary fats into sensory experiences has profound implications for nutritional well-being. This study presents an efficient approach to comprehending the neural perception of fat taste using electroencephalogram (EEG). Through the examination of neural responses to different types of fatty acids (FAs) in 45 participants, we discerned distinct neural activation patterns associated with saturated versus unsaturated fatty acids. The spectrum analysis of averaged EEG signals revealed notable variations in δ and α-frequency bands across FA types. The topographical distribution and source localization results suggested that the brain encodes fat taste with specific activation timings in primary and secondary gustatory cortices. Saturated FAs elicited higher activation in cortical associated with emotion and reward processing. This electrophysiological evidence enhances our understanding of fundamental mechanisms behind fat perception, which is helpful for guiding strategies to manage hedonic eating and promote balanced fat consumption.


Subject(s)
Brain , Dietary Fats , Electroencephalography , Taste Perception , Humans , Female , Young Adult , Adult , Male , Brain/physiology , Dietary Fats/metabolism , Dietary Fats/analysis , Taste , Fatty Acids/chemistry , Fatty Acids/metabolism
5.
Article in English | MEDLINE | ID: mdl-38657943

ABSTRACT

In mammals, physiological processes related to lipid metabolism, such as chylomicron synthesis or fatty acid oxidation (FAO), modulate eating, highlighting the importance of energostatic mechanisms in feeding control. This study, using rainbow trout (Oncorhynchus mykiss) as model, aimed to characterize the role of FAO and chylomicron formation as peripheral lipid sensors potentially able to modulate feeding in fish. Fish fed with either a normal- (24%) or high- (32%) fat diet were intraperitoneally injected with water alone or containing etomoxir (inhibitor of FAO rate-limiting enzyme carnitine palmitoyl-transferase 1). First, feed intake levels were recorded. We observed an etomoxir-derived decrease in feeding at short times, but a significant increase at 48 h after treatment in fish fed normal-fat diet. Then, we evaluated putative etomoxir effects on the mRNA abundance of genes related to lipid metabolism, chylomicron synthesis and appetite-regulating peptides. Etomoxir treatment upregulated mRNA levels of genes related to chylomicron assembly in proximal intestine, while opposite effects occurred in distal intestine, indicating a clear regionalization in response. Etomoxir also modulated gastrointestinal hormone mRNAs in proximal intestine, upregulating ghrl in fish fed normal-fat diet and pyy and gcg in fish fed high-fat diet. These results provide evidence for an energostatic control of feeding related to FAO and chylomicron formation at the peripheral level in fish.


Subject(s)
Chylomicrons , Dietary Fats , Fatty Acids , Lipid Metabolism , Oncorhynchus mykiss , Oxidation-Reduction , Animals , Oncorhynchus mykiss/metabolism , Fatty Acids/metabolism , Chylomicrons/metabolism , Dietary Fats/metabolism , Dietary Fats/pharmacology , Gastrointestinal Tract/metabolism , Epoxy Compounds/metabolism , Epoxy Compounds/pharmacology , Carnitine O-Palmitoyltransferase/metabolism , Carnitine O-Palmitoyltransferase/genetics
6.
Genes (Basel) ; 15(4)2024 Apr 10.
Article in English | MEDLINE | ID: mdl-38674414

ABSTRACT

Carnitine acetyltransferase (CAT) and Enoyl-CoA hydratase short-chain 1 (ECHS1) are considered key enzymes that regulate the ß-oxidation of fatty acids. However, very few studies have investigated their full length and expression in genetically improved farmed tilapia (GIFT, Oreochromis niloticus), an important aquaculture species in China. Here, we cloned CAT and ECHS1 full-length cDNA via the rapid amplification of cDNA ends, and the expressions of CAT and ECHS1 in the liver of juvenile GIFT were detected in different fat and carnitine diets, as were the changes in the lipometabolic enzymes and serum biochemical indexes of juvenile GIFT in diets with different fat and carnitine levels. CAT cDNA possesses an open reading frame (ORF) of 2167 bp and encodes 461 amino acids, and the ECHS1 cDNA sequence is 1354 bp in full length, the ORF of which encodes a peptide of 391 amino acids. We found that juvenile GIFT had higher lipometabolic enzyme activity and lower blood CHOL, TG, HDL-C, and LDL-C contents when the dietary fat level was 2% or 6% and when the carnitine level was 500 mg/kg. We also found that the expression of ECHS1 and CAT genes in the liver of juvenile GIFT can be promoted by a 500 mg/kg carnitine level and 6% fat level feeding. These results suggested that CAT and ECHS1 may participate in regulating lipid metabolism, and when 2% or 6% fat and 500 mg/kg carnitine are added to the feed, it is the most beneficial to the liver and lipid metabolism of juvenile GIFT. Our results may provide a theoretical basis for GIFT feeding and treating fatty liver disease.


Subject(s)
Carnitine O-Acetyltransferase , Carnitine , Enoyl-CoA Hydratase , Liver , Animals , Liver/metabolism , Carnitine/metabolism , Carnitine O-Acetyltransferase/genetics , Carnitine O-Acetyltransferase/metabolism , Enoyl-CoA Hydratase/genetics , Enoyl-CoA Hydratase/metabolism , Cichlids/genetics , Cichlids/metabolism , Cichlids/growth & development , Dietary Fats/pharmacology , Dietary Fats/metabolism , Fish Proteins/genetics , Fish Proteins/metabolism , Lipid Metabolism/genetics
7.
Mol Metab ; 82: 101913, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38458567

ABSTRACT

OBJECTIVE: Adipose tissue mass is maintained by a balance between lipolysis and lipid storage. The contribution of adipose tissue lipogenesis to fat mass, especially in the setting of high-fat feeding, is considered minor. Here we investigated the effect of adipose-specific inactivation of the peroxisomal lipid synthetic protein PexRAP on fatty acid synthase (FASN)-mediated lipogenesis and its impact on adiposity and metabolic homeostasis. METHODS: To explore the role of PexRAP in adipose tissue, we metabolically phenotyped mice with adipose-specific knockout of PexRAP. Bulk RNA sequencing was used to determine transcriptomic responses to PexRAP deletion and 14C-malonyl CoA allowed us to measure de novo lipogenic activity in adipose tissue of these mice. In vitro cell culture models were used to elucidate the mechanism of cellular responses to PexRAP deletion. RESULTS: Adipose-specific PexRAP deletion promoted diet-induced obesity and insulin resistance through activation of de novo lipogenesis. Mechanistically, PexRAP inactivation inhibited the flux of carbons to ethanolamine plasmalogens. This increased the nuclear PC/PE ratio and promoted cholesterol mislocalization, resulting in activation of liver X receptor (LXR), a nuclear receptor known to be activated by increased intracellular cholesterol. LXR activation led to increased expression of the phospholipid remodeling enzyme LPCAT3 and induced FASN-mediated lipogenesis, which promoted diet-induced obesity and insulin resistance. CONCLUSIONS: These studies reveal an unexpected role for peroxisome-derived lipids in regulating LXR-dependent lipogenesis and suggest that activation of lipogenesis, combined with dietary lipid overload, exacerbates obesity and metabolic dysregulation.


Subject(s)
Insulin Resistance , Lipogenesis , Animals , Mice , 1-Acylglycerophosphocholine O-Acyltransferase/metabolism , Adipose Tissue/metabolism , Cholesterol/metabolism , Dietary Fats/metabolism , Lipogenesis/genetics , Liver X Receptors/metabolism , Mice, Knockout , Obesity/metabolism
8.
Food Chem ; 448: 139054, 2024 Aug 01.
Article in English | MEDLINE | ID: mdl-38552465

ABSTRACT

Quercetin (QUE) sufferred from poor processing adaptability and absorbability, hindering its application as a dietary supplement in the food industry. In this study, fatty acids (FAs)-sodium caseinate (NaCas) ligand complexes carriers were fabricated to improve the aqueous dispersibility, storage/thermal stability, and bioaccessibility of QUE using an ultrasound method. The results indicated that all six selected common dietary FAs formed stable hydrophilic complexes with NaCas and the FAs-NaCas complexes achieved an encapsulation efficiency greater than 90 % for QUE. Furthermore, the introduction of FAs enhanced the binding affinity between NaCas and QUE, but did not change the binding mode (static bursting) and types of intermolecular forces (mainly hydrogen bonding). In addition, a distinct improvement was discovered in the storage stability (>2.37-fold), thermal processing stability (>32.54 %), and bioaccessibility (>2.37-fold) of QUE. Therefore, the FAs-NaCas ligand complexes could effectively protect QUE to minimize degradation as fat-soluble polyphenol delivery vehicles.


Subject(s)
Caseins , Fatty Acids , Quercetin , Quercetin/chemistry , Quercetin/metabolism , Fatty Acids/chemistry , Fatty Acids/metabolism , Caseins/chemistry , Caseins/metabolism , Drug Stability , Biological Availability , Humans , Hydrophobic and Hydrophilic Interactions , Water/chemistry , Dietary Fats/metabolism
9.
Nat Commun ; 15(1): 2382, 2024 Mar 16.
Article in English | MEDLINE | ID: mdl-38493217

ABSTRACT

Maternal overnutrition during lactation predisposes offspring to develop metabolic diseases and exacerbates the relevant syndromes in males more than females in later life. The hypothalamus is a heterogenous brain region that regulates energy balance. Here we combined metabolic trait quantification of mother and offspring mice under low and high fat diet (HFD) feeding during lactation, with single nucleus transcriptomic profiling of their offspring hypothalamus at peak lacation to understand the cellular and molecular alterations in response to maternal dietary pertubation. We found significant expansion in neuronal subpopulations including histaminergic (Hdc), arginine vasopressin/retinoic acid receptor-related orphan receptor ß (Avp/Rorb) and agouti-related peptide/neuropeptide Y (AgRP/Npy) in male offspring when their mothers were fed HFD, and increased Npy-astrocyte interactions in offspring responding to maternal overnutrition. Our study provides a comprehensive offspring hypothalamus map at the peak lactation and reveals how the cellular subpopulations respond to maternal dietary fat in a sex-specific manner during development.


Subject(s)
Dietary Fats , Obesity , Humans , Female , Mice , Male , Animals , Dietary Fats/metabolism , Obesity/metabolism , Hypothalamus/metabolism , Diet, High-Fat/adverse effects , Neuropeptide Y/metabolism , Lactation , Gene Expression Profiling , Maternal Nutritional Physiological Phenomena
10.
Nat Commun ; 15(1): 2102, 2024 Mar 07.
Article in English | MEDLINE | ID: mdl-38453901

ABSTRACT

Nicotinamide adenine dinucleotide (NAD)+ serves as a crucial coenzyme in numerous essential biological reactions, and its cellular availability relies on the activity of the nicotinamide phosphoribosyltransferase (NAMPT)-catalyzed salvage pathway. Here we show that treatment with saturated fatty acids activates the NAD+ salvage pathway in hypothalamic astrocytes. Furthermore, inhibition of this pathway mitigates hypothalamic inflammation and attenuates the development of obesity in male mice fed a high-fat diet (HFD). Mechanistically, CD38 functions downstream of the NAD+ salvage pathway in hypothalamic astrocytes burdened with excess fat. The activation of the astrocytic NAMPT-NAD+-CD38 axis in response to fat overload induces proinflammatory responses in the hypothalamus. It also leads to aberrantly activated basal Ca2+ signals and compromised Ca2+ responses to metabolic hormones such as insulin, leptin, and glucagon-like peptide 1, ultimately resulting in dysfunctional hypothalamic astrocytes. Our findings highlight the significant contribution of the hypothalamic astrocytic NAD+ salvage pathway, along with its downstream CD38, to HFD-induced obesity.


Subject(s)
Dietary Fats , NAD , Male , Mice , Animals , NAD/metabolism , Dietary Fats/metabolism , Astrocytes/metabolism , Obesity/metabolism , Hypothalamus/metabolism , Cytokines/metabolism
11.
Sci Rep ; 14(1): 5610, 2024 03 07.
Article in English | MEDLINE | ID: mdl-38453966

ABSTRACT

Given that ketogenic diets (KDs) are extremely high in dietary fat, we compared different fats in KDs to determine which was the best for cancer prevention. Specifically, we compared a Western and a 15% carbohydrate diet to seven different KDs, containing either Western fats or fats enriched in medium chain fatty acids (MCTs), milk fat (MF), palm oil (PO), olive oil (OO), corn oil (CO) or fish oil (FO) for their ability to reduce nicotine-derived nitrosamine ketone (NNK)-induced lung cancer in mice. While all the KDs tested were more effective at reducing lung nodules than the Western or 15% carbohydrate diet, the FO-KD was most effective at reducing lung nodules. Correlating with this, mice on the FO-KD had low blood glucose and the highest ß-hydroxybutyrate level, lowest liver fatty acid synthase/carnitine palmitoyl-1a ratio and a dramatic increase in fecal Akkermansia. We found no liver damage induced by the FO-KD, while the ratio of total cholesterol/HDL was unchanged on the different diets. We conclude that a FO-KD is superior to KDs enriched in other fats in reducing NNK-induced lung cancer, perhaps by being the most effective at skewing whole-body metabolism from a dependence on glucose to fats as an energy source.


Subject(s)
Diet, Ketogenic , Dietary Fats, Unsaturated , Lung Neoplasms , Mice , Animals , Fish Oils/pharmacology , Fish Oils/metabolism , Dietary Fats, Unsaturated/metabolism , Plant Oils/pharmacology , Plant Oils/metabolism , Lung Neoplasms/chemically induced , Lung Neoplasms/prevention & control , Dietary Fats/metabolism , Olive Oil , Diet , Carbohydrates
12.
Obesity (Silver Spring) ; 32(4): 733-742, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38410048

ABSTRACT

OBJECTIVE: High-fat diets cause obesity in male mice; however, the underlying mechanisms remain controversial. Here, three contrasting ideas were assessed: hedonic overdrive, reverse causality, and passive overconsumption models. METHODS: A total of 12 groups of 20 individually housed 12-week-old C57BL/6 male mice were exposed to 12 high-fat diets with varying fat content from 40% to 80% (by calories), protein content from 5% to 30%, and carbohydrate content from 8.4% to 40%. Body weight and food intake were monitored for 30 days after 7 days at baseline on a standard low-fat diet. RESULTS: After exposure to the diets, energy intake increased first, and body weight followed later. Intake then declined. The peak energy intake was dependent on both dietary protein and carbohydrate, but not the dietary fat and energy density, whereas the rate of decrease in intake was only related to dietary protein. On high-fat diets, the weight of food intake declined, but despite this average reduction of 14.4 g in food intake, they consumed, on average, 357 kJ more energy than at baseline. CONCLUSIONS: The hedonic overdrive model fit the data best. The other two models were not supported.


Subject(s)
Diet, High-Fat , Dietary Carbohydrates , Male , Mice , Animals , Diet, High-Fat/adverse effects , Dietary Carbohydrates/metabolism , Mice, Inbred C57BL , Obesity/etiology , Obesity/metabolism , Dietary Fats/metabolism , Energy Intake , Dietary Proteins
13.
Cell ; 187(5): 1177-1190.e18, 2024 Feb 29.
Article in English | MEDLINE | ID: mdl-38366593

ABSTRACT

Phospholipids containing a single polyunsaturated fatty acyl tail (PL-PUFA1s) are considered the driving force behind ferroptosis, whereas phospholipids with diacyl-PUFA tails (PL-PUFA2s) have been rarely characterized. Dietary lipids modulate ferroptosis, but the mechanisms governing lipid metabolism and ferroptosis sensitivity are not well understood. Our research revealed a significant accumulation of diacyl-PUFA phosphatidylcholines (PC-PUFA2s) following fatty acid or phospholipid treatments, correlating with cancer cell sensitivity to ferroptosis. Depletion of PC-PUFA2s occurred in aging and Huntington's disease brain tissue, linking it to ferroptosis. Notably, PC-PUFA2s interacted with the mitochondrial electron transport chain, generating reactive oxygen species (ROS) for initiating lipid peroxidation. Mitochondria-targeted antioxidants protected cells from PC-PUFA2-induced mitochondrial ROS (mtROS), lipid peroxidation, and cell death. These findings reveal a critical role for PC-PUFA2s in controlling mitochondria homeostasis and ferroptosis in various contexts and explain the ferroptosis-modulating mechanisms of free fatty acids. PC-PUFA2s may serve as diagnostic and therapeutic targets for modulating ferroptosis.


Subject(s)
Dietary Fats , Ferroptosis , Phospholipids , Fatty Acids , Phosphatidylcholines , Phospholipids/chemistry , Phospholipids/metabolism , Reactive Oxygen Species , Dietary Fats/metabolism
14.
Food Funct ; 15(4): 1803-1824, 2024 Feb 19.
Article in English | MEDLINE | ID: mdl-38314832

ABSTRACT

Cognitive impairment, as a prevalent symptom of nervous system disorders, poses one of the most challenging aspects in the management of brain diseases. Lipids present in the cell membranes of all neurons within the brain and dietary lipids can regulate the cognition and memory function. In recent years, the advancements in gut microbiome research have enabled the exploration of dietary lipids targeting the gut-brain axis as a strategy for regulating cognition. This present review provides an in-depth overview of how lipids modulate cognition via the gut-brain axis depending on metabolic, immune, neural and endocrine pathways. It also comprehensively analyzes the effects of diverse lipids on the gut microbiota and intestinal barrier function, thereby affecting the central nervous system and cognitive capacity. Moreover, comparative analysis of the positive and negative effects is presented between beneficial and detrimental lipids. The former encompass monounsaturated fatty acids, short-chain fatty acids, omega-3 polyunsaturated fatty acids, phospholipids, phytosterols, fungal sterols and bioactive lipid-soluble vitamins, as well as lipid-derived gut metabolites, whereas the latter (detrimental lipids) include medium- or long-chain fatty acids, excessive proportions of n-6 polyunsaturated fatty acids, industrial trans fatty acids, and zoosterols. To sum up, the focus of this review is on how gut-brain communication mediates the impact of dietary lipids on cognitive capacity, providing a novel theoretical foundation for promoting brain cognitive health and scientific lipid consumption patterns.


Subject(s)
Dietary Fats , Fatty Acids, Omega-3 , Dietary Fats/metabolism , Fatty Acids/metabolism , Brain/metabolism , Fatty Acids, Omega-3/metabolism , Cognition
15.
Eur J Nutr ; 63(2): 539-548, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38093120

ABSTRACT

PURPOSE: Longer-term intake of fatty acid (FA)-modified dairy products (SFA-reduced, MUFA-enriched) was reported to attenuate postprandial endothelial function in humans, relative to conventional (control) dairy. Thus, we performed an in vitro study in human aortic endothelial cells (HAEC) to investigate mechanisms underlying the effects observed in vivo. METHODS: This sub-study was conducted within the framework of the RESET study, a 12-week randomised controlled crossover trial with FA-modified and control dairy diets. HAEC were incubated for 24 h with post-intervention plasma samples from eleven adults (age: 57.5 ± 6.0 years; BMI: 25.7 ± 2.7 kg/m2) at moderate cardiovascular disease risk following representative sequential mixed meals. Markers of endothelial function and lipid regulation were assessed. RESULTS: Relative to control, HAEC incubation with plasma following the FA-modified treatment increased postprandial NOx production (P-interaction = 0.019), yet up-regulated relative E-selectin mRNA gene expression (P-interaction = 0.011). There was no impact on other genes measured. CONCLUSION: Incubation of HAEC with human plasma collected after longer-term dairy fat manipulation had a beneficial impact on postprandial NOx production. Further ex vivo research is needed to understand the impact of partial replacement of SFA with unsaturated fatty acids in dairy foods on pathways involved in endothelial function.


Subject(s)
Endothelial Cells , Fatty Acids , Adult , Humans , Middle Aged , Endothelial Cells/metabolism , Fatty Acids/pharmacology , Fatty Acids, Unsaturated , Diet , Dairy Products , Postprandial Period , Dietary Fats/metabolism , Cross-Over Studies
16.
Obesity (Silver Spring) ; 32(1): 12-22, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37846155

ABSTRACT

The pathogenesis of obesity remains contested. Although genetics is important, the rapid rise in obesity with Western culture and diet suggests an environmental component. Today, some of the major hypotheses for obesity include the energy balance hypothesis, the carbohydrate-insulin model, the protein-leverage hypothesis, and the seed oil hypothesis. Each hypothesis has its own support, creating controversy over their respective roles in driving obesity. Here we propose that all hypotheses are largely correct and can be unified by another dietary hypothesis, the fructose survival hypothesis. Fructose is unique in resetting ATP levels to a lower level in the cell as a consequence of suppressing mitochondrial function, while blocking the replacement of ATP from fat. The low intracellular ATP levels result in carbohydrate-dependent hunger, impaired satiety (leptin resistance), and metabolic effects that result in the increased intake of energy-dense fats. This hypothesis emphasizes the unique role of carbohydrates in stimulating intake while fat provides the main source of energy. Thus, obesity is a disorder of energy metabolism, in which there is low usable energy (ATP) in the setting of elevated total energy. This leads to metabolic effects independent of excess energy while the excess energy drives weight gain.


Subject(s)
Fructose , Obesity , Humans , Obesity/metabolism , Weight Gain , Diet , Energy Metabolism , Adenosine Triphosphate/metabolism , Dietary Fats/metabolism , Dietary Carbohydrates/metabolism , Energy Intake
17.
Br J Nutr ; 131(3): 447-460, 2024 02 14.
Article in English | MEDLINE | ID: mdl-37578022

ABSTRACT

The present study investigated the potential role of the composition of dietary fatty acids in the regulation of biological rhythms, such as the sleep architecture, core body temperature and leukocyte clock gene expression, in subjects fed meals rich in palmitic acid (PA) or oleic acid (OA). Eleven males participated in two sessions of indirect calorimetry in a whole-room metabolic chamber. In each session, subjects consumed three meals rich in PA (44·3 % of total fat as PA and 42·3 % as OA) or OA (11·7 % of total fat as PA and 59·3 % as OA) in the metabolic chamber. The ratio of PA to OA in plasma was significantly lower and fat oxidation was significantly higher during 24 h of indirect calorimetry in the session with meals rich in OA than in that with meals rich in PA. The duration of slow wave sleep (SWS) was shorter, the latency of SWS was longer and the nadir of core body temperature after bedtime was later in the session with meals rich in PA than in that with meals rich in OA. The peak in CRY1 gene expression was earlier and its amplitude was higher in the session with meals rich in PA than in that with meals rich in OA. In healthy young males, meals rich in PA decreased fat oxidation and disrupted biological rhythms, particularly the sleep architecture and core body temperature during sleep, more than meals rich in OA.


Subject(s)
Oleic Acid , Palmitic Acid , Male , Humans , Japan , Energy Metabolism , Periodicity , Dietary Fats/metabolism
18.
Article in English | MEDLINE | ID: mdl-38056555

ABSTRACT

Diet shifts can alter tissue fatty acid composition in birds, which is subsequently related to metabolic patterns. Eicosanoids, short-lived fatty acid-derived hormones, have been proposed to mediate these relationships but neither baseline concentrations nor the responses to diet and exercise have been measured in songbirds. We quantified a stable derivative of the vasodilatory eicosanoid prostacyclin in the plasma of male European Starlings (Sturnus vulgaris, N = 25) fed semisynthetic diets with either high (PUFA) or low (MUFA) amounts of n6 fatty acid precursors to prostacyclin. Plasma samples were taken from each bird before, immediately after, and two days following a 15-day flight-training regimen that a subset of birds (N = 17) underwent. We found elevated prostacyclin levels in flight-trained birds fed the PUFA diet compared to those fed the MUFA diet and a positive relationship between prostacyclin and body condition, indexed by fat score. Prostacyclin concentrations also significantly decreased at the final time point. These results are consistent with the proposed influences of precursor availability (i.e., dietary fatty acids) and regulatory feedback associated with exercise (i.e., fuel supply and inflammation), and suggest that prostacyclin may be an important mediator of dietary influence on songbird physiology.


Subject(s)
Epoprostenol , Songbirds , Male , Animals , Songbirds/metabolism , Fatty Acids , Eicosanoids , Hormones , Dietary Fats/metabolism
19.
Nature ; 625(7994): 385-392, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38123683

ABSTRACT

Digested dietary fats are taken up by enterocytes where they are assembled into pre-chylomicrons in the endoplasmic reticulum followed by transport to the Golgi for maturation and subsequent secretion to the circulation1. The role of mitochondria in dietary lipid processing is unclear. Here we show that mitochondrial dysfunction in enterocytes inhibits chylomicron production and the transport of dietary lipids to peripheral organs. Mice with specific ablation of the mitochondrial aspartyl-tRNA synthetase DARS2 (ref. 2), the respiratory chain subunit SDHA3 or the assembly factor COX10 (ref. 4) in intestinal epithelial cells showed accumulation of large lipid droplets (LDs) in enterocytes of the proximal small intestine and failed to thrive. Feeding a fat-free diet suppressed the build-up of LDs in DARS2-deficient enterocytes, which shows that the accumulating lipids derive mostly from digested fat. Furthermore, metabolic tracing studies revealed an impaired transport of dietary lipids to peripheral organs in mice lacking DARS2 in intestinal epithelial cells. DARS2 deficiency caused a distinct lack of mature chylomicrons concomitant with a progressive dispersal of the Golgi apparatus in proximal enterocytes. This finding suggests that mitochondrial dysfunction results in impaired trafficking of chylomicrons from the endoplasmic reticulum to the Golgi, which in turn leads to storage of dietary lipids in large cytoplasmic LDs. Taken together, these results reveal a role for mitochondria in dietary lipid transport in enterocytes, which might be relevant for understanding the intestinal defects observed in patients with mitochondrial disorders5.


Subject(s)
Dietary Fats , Enterocytes , Lipid Metabolism , Mitochondria , Animals , Mice , Aspartate-tRNA Ligase/metabolism , Chylomicrons/metabolism , Dietary Fats/metabolism , Electron Transport Complex II/metabolism , Endoplasmic Reticulum/metabolism , Enterocytes/metabolism , Enterocytes/pathology , Epithelial Cells/metabolism , Golgi Apparatus/metabolism , Intestines , Lipid Droplets/metabolism , Mitochondria/metabolism , Mitochondria/pathology
20.
J Nutr ; 154(3): 856-865, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38160803

ABSTRACT

BACKGROUND: Hepatic mitochondrial dysfunction is a major cause of fat accumulation in the liver. Individuals with fatty liver conditions have hepatic mitochondrial structural abnormalities and a switch in the side chain composition of the mitochondrial phospholipid, cardiolipin, from poly- to monounsaturated fatty acids. Linoleic acid (LA), an essential dietary fatty acid, is required to remodel nascent cardiolipin (CL) to its tetralinoleoyl cardiolipin (L4CL, CL with 4 LA side chains) form, which is integral for mitochondrial membrane structure and function to promote fatty acid oxidation. It is unknown, however, whether increasing LA in the diet can increase hepatic L4CL concentrations and improve mitochondrial respiration in the liver compared with a diet rich in monounsaturated and saturated fatty acids. OBJECTIVES: The main aim of this study was to test the ability of a diet fortified with LA-rich safflower oil (SO), compared with the one fortified with lard (LD), to increase concentrations of L4CL and improve mitochondrial respiration in the livers of mice. METHODS: Twenty-four (9-wk-old) C57 BL/J6 male mice were fed either the SO or LD diets for ∼100 d, whereas food intake and body weight, fasting glucose, and glucose tolerance tests were performed to determine any changes in glycemic control. RESULTS: Livers from mice fed SO diet had higher relative concentrations of hepatic L4CL species compared with LD diet-fed mice (P value = 0.004). Uncoupled mitochondria of mice fed the SO diet, compared with LD diet, had an increased baseline oxygen consumption rate (OCR) and succinate-driven respiration (P values = 0.03 and 0.01). SO diet-fed mice had increased LA content in all phospholipid classes compared with LD-fed mice (P < 0.05). CONCLUSIONS: Our findings reveal that maintaining or increasing hepatic L4CL may result in increased OCR in uncoupled hepatic mitochondria in healthy mice whereas higher oleate content of CL reduced mitochondrial function shown by lower OCR in uncoupled mitochondria.


Subject(s)
Cardiolipins , Linoleic Acid , Male , Mice , Animals , Cardiolipins/metabolism , Mitochondria , Dietary Fats/metabolism , Fatty Acids/metabolism , Liver/metabolism , Diet , Phospholipids/metabolism , Linoleic Acids/metabolism , Respiration
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