Adipose Tissue Insulin Resistance in South Asian and Nordic Women after Gestational Diabetes Mellitus.

South Asians (SAs) have a higher risk of developing type 2 diabetes (T2D) than white Europeans, especially following gestational diabetes mellitus (GDM). Despite similar blood glucose levels post-GDM, SAs exhibit more insulin resistance (IR) than Nordics, though the underlying mechanisms are unclear. This study aimed to assess markers of adipose tissue (AT) IR and liver fat in SA and Nordic women post-GDM. A total of 179 SA and 108 Nordic women in Norway underwent oral glucose tolerance tests 1-3 years post-GDM. We measured metabolic markers and calculated the AT IR index and non-alcoholic fatty liver disease liver fat (NAFLD-LFS) scores. Results showed that normoglycaemic SAs had less non-esterified fatty acid (NEFA) suppression during the test, resembling prediabetes/T2D responses, and higher levels of plasma fetuin-A, CRP, and IL-6 but lower adiponectin, indicating AT inflammation. Furthermore, normoglycaemic SAs had higher NAFLD-LFS scores, lower insulin clearance, and higher peripheral insulin than Nordics, indicating increased AT IR, inflammation, and liver fat in SAs. Higher liver fat markers significantly contributed to the ethnic disparities in glucose metabolism, suggesting a key area for intervention to reduce T2D risk post-GDM in SAs.

The Protective Role of Vitamin E against Oxidative Stress and Immunosuppression Induced by Non-Esterified Fatty Acids in Bovine Peripheral Blood Leukocytes.

High levels of non-esterified fatty acids (NEFAs) during the transition period lead to increased oxidative stress and immunosuppression in cows. Feeding them a vitamin-E-supplemented diet reduces reactive oxygen species (ROS) levels in the blood and diminishes immunosuppression in the transition period. However, whether the restoration of immune cell function occurs through the direct action of vitamin E in cells is still a topic that requires further discussion. Therefore, in this experiment, we aimed to investigate the effect of NEFAs on peripheral blood leukocytes (PBLs) and whether vitamin E mitigates the impact of NEFAs. We employed three groups: (1) blank, (2) NEFA only, and (3) pre-culturing with vitamin E before NEFA treatment (VENEFA). In peripheral blood mononuclear cells (PBMCs), there were no differences in vitamin E content among the three groups. However, in the vitamin E pre-treatment group, the vitamin E levels of polymorphonuclear neutrophils (PMNs) were significantly higher than those in the other two groups. NEFA levels increased malondialdehyde (MDA) levels in PBMCs, but pre-treatment with vitamin E reduced accumulation of MDA levels. Regarding the expression of proinflammatory genes, NEFAs increased the expression of interleukin-1ß in PBMCs and colony-stimulating factor 2 in PMNs. Vitamin E pre-treatment restored the increase in interleukin-1ß levels caused by NEFAs in PBMCs. None of the groups affected the phagocytosis of PMNs. Few studies have confirmed that NEFAs cause oxidative stress in bovine PBLs. In summary, this study found that NEFAs induce oxidative stress in PBLs and alter the expression of inflammation-related genes; meanwhile, vitamin E can reduce some of the effects caused by NEFAs. This result may suggest that vitamin E can assist bovine PBLs in resisting the immune suppression caused by an NEB during the transition period.

Effects of Summer Heat on Adipose Tissue Activity in Periparturient Simmental Cows.

Hot climate is one of the major factors affecting the dairy industry. Heat stress could be responsible for decreased feed intake and consequently leads to alterations in energy metabolism, particularly during late pregnancy and early lactation. This study aimed to assess the effects of summer heat on adipose tissue activities during the periparturient period in Simmental cows. Two groups of cows were involved: heat-stressed cows (n = 12) that calved from June to August and thermoneutral cows (n = 12) that calved from October to December. Blood samples were taken from each cow during the periparturient period: 21 and 7 days before calving and 8, 16, 24, 32, and 40 days after calving. Glucose, beta-hydroxy butyrate (BHB), non-esterified fatty acids (NEFA), leptin (LP), and adiponectin (ADP) were measured in serum samples by commercial kits. Thermoneutral cows expressed higher degrees of lipomobilization syndrome than heat-stressed cows, indicated by significantly higher serum NEFA and BHB concentrations in the early lactation. Leptin levels were significantly decreased, while adiponectin was increased in heat-stressed cows compared to thermoneutral ones. The results indicated that heat-stressed cows during the periparturient period mobilized less fat from adipose tissue to reduce the heat generation by fatty acid oxidation.

Lactation performance, feed efficiency, and blood metabolites of dairy cows treated with recombinant bovine somatotropin: A systematic review and meta-analysis.

A systematic review and meta-analysis were conducted to assess the impact of recombinant bovine somatotropin (rbST) on lactation performance, feed efficiency, and blood metabolites in dairy cows. In the systematic review, articles were selected based on the following criteria: (1) Data focusing on the influence of bovine somatotropin doses on milk production; (2) Submission of original data; (3) Articles published in journals; and (4) Articles in English or Portuguese. The analysis of variance was used with a completely randomized design and mixed models methodology. Polynomial regression was applied to significant fixed effects (rbST dose). The use of rbST resulted in increased milk yield and 4% fat-corrected milk yield, while fat, protein, and lactose contents remained unaffected. Dry matter and metabolizable energy intakes, as well as milk/feed efficiency, exhibited a linear increase, but body condition score (BCS) was negatively impacted. The administration of rbST led to higher blood concentrations of triglycerides and insulin. Cows treated with rbST showed a 23% increase in non-esterified fatty acid (NEFA) concentrations compared to non-treated cows. Additionally, growth factors IGF-1 and IGF-2 displayed a linear increase with rbST treatment. In summary, rbST administration increased milk yield and fat-corrected milk yield without affecting milk components. However, despite increasing intake, it resulted in BCS losses and alterations in blood parameters such as NEFA, IGF-1, and IGF-2.

Effects of hypertriglyceridemia with or without NEFA elevation on ß-cell function and insulin clearance and sensitivity.

AIMS: Hypertriglyceridemia is a risk factor for developing type 2 diabetes (T2D) and might contribute to its pathogenesis either directly or through elevation of non-esterified fatty acids (NEFAs). This study aimed at comparing the glucometabolic effects of acute hypertriglyceridemia alone or combined with NEFA elevation in non-diabetic subjects. METHODS: Twenty-two healthy lean volunteers underwent two 5-h intravenous infusions of either saline or Intralipid, without (n=12) or with heparin (I+H; n=10) to activate the release of NEFAs. Oral glucose tolerance tests (OGTTs) were performed during the last 3h of infusion. Insulin sensitivity, insulin secretion rate (ISR), model-derived ß-cell function, and insulin clearance were measured after 2h of lipid infusion and during the OGTTs. RESULTS: In fasting conditions, both lipid infusions increased plasma insulin and ISR and reduced insulin clearance, without affecting plasma glucose and insulin sensitivity. These effects on insulin and ISR were more pronounced for I+H than Intralipid alone. During the OGTT, the lipid infusions markedly impaired glucose tolerance, increased plasma insulin and ISR, and decreased insulin sensitivity and clearance, without significant group differences. Intralipid alone inhibited glucose-stimulated insulin secretion (i.e. ß-cell glucose sensitivity) and increased ß-cell potentiation, whereas I+H had neutral effects on these ß-cell functions. CONCLUSION: In healthy non-obese subjects, mild acute hypertriglyceridemia directly reduces glucose tolerance, insulin sensitivity and clearance, and has selective and opposite effects on ß-cell function that are neutralized by NEFAs. These findings provide new insight into plausible biological signals that generate and sustain insulin resistance and chronic hyperinsulinemia in the development of T2D.

Highland deer mice support increased thermogenesis in response to chronic cold hypoxia by shifting uptake of circulating fatty acids from muscles to brown adipose tissue.

During maximal cold challenge (cold-induced V̇O2,max) in hypoxia, highland deer mice (Peromyscus maniculatus) show higher rates of circulatory fatty acid delivery compared with lowland deer mice. Fatty acid delivery also increases with acclimation to cold hypoxia (CH) and probably plays a major role in supporting the high rates of thermogenesis observed in highland deer mice. However, it is unknown which tissues take up these fatty acids and their relative contribution to thermogenesis. The goal of this study was to determine the uptake of circulating fatty acids into 24 different tissues during hypoxic cold-induced V̇O2,max, by using [1-14C]2-bromopalmitic acid. To uncover evolved and environment-induced changes in fatty acid uptake, we compared lab-born and -raised highland and lowland deer mice, acclimated to either thermoneutral (30°C, 21 kPa O2) or CH (5°C, 12 kPa O2) conditions. During hypoxic cold-induced V̇O2,max, CH-acclimated highlanders decreased muscle fatty acid uptake and increased uptake into brown adipose tissue (BAT) relative to thermoneutral highlanders, a response that was absent in lowlanders. CH acclimation was also associated with increased activities of enzymes citrate synthase and ß-hydroxyacyl-CoA dehydrogenase in the BAT of highlanders, and higher levels of fatty acid translocase CD36 (FAT/CD36) in both populations. This is the first study to show that cold-induced fatty acid uptake is distributed across a wide range of tissues. Highland deer mice show plasticity in this fatty acid distribution in response to chronic cold hypoxia, and combined with higher rates of tissue delivery, this contributes to their survival in the cold high alpine environment.

NEFA can serve as good biological markers for the diagnosis of depression in adolescents.

BACKGROUND: The incidence of adolescent depression has markedly risen in recent years, with a high recurrence rate into adulthood. Diagnosis in adolescents is challenging due to subjective factors, highlighting the crucial need for objective diagnostic markers. METHODS: Our study enrolled 204 participants, including healthy controls (n = 88) and first-episode adolescent depression patients (n = 116). Serum samples underwent gas chromatography-mass spectrometry (GC-MS) analysis to assess non-esterified fatty acids (NEFA) expression. Machine learning and ROC analysis were employed to identify potential biomarkers, followed by bioinformatics analysis to explore underlying mechanisms. RESULTS: Nearly all differentially expressed NEFA exhibited significant downregulation. Notably, nonanoic acid, cis-10-pentadecenoic acid, cis-10-carboenoic acid, and cis-11-eicosenoic acid demonstrated excellent performance in distinguishing adolescent depression patients. Metabolite-gene interaction analysis revealed these NEFAs interacted with multiple genes. KEGG pathway analysis on these genes suggested that differentially expressed NEFA may impact PPAR and cAMP signaling pathways. LIMITATIONS: Inclusion of diverse populations for evaluation is warranted. Biomarkers identified in this study require samples that are more in line with the experimental design for external validation, and further basic research is necessary to validate the potential depressive mechanisms of NEFA. CONCLUSIONS: The overall reduction in NEFA expression in first-episode adolescent depression patients suggests a potential mediation of depression symptoms through cAMP and PPAR signaling pathways. NEFA levels show promise as a diagnostic tool for identifying first-episode adolescent depression patients.

Higher circulating levels of non-esterified fatty acids are associated with faster kidney function decline in post-menopausal women with type 2 diabetes: a pilot prospective study.

AIMS: Currently, there is little and inconsistent evidence regarding the possible adverse effects of circulating levels of non-esterified fatty acids (NEFA) on kidney function decline in patients with type 2 diabetes mellitus (T2DM). METHODS: We followed for a median of 4.6 years 85 post-menopausal women with non-insulin-treated T2DM and preserved kidney function at baseline. Serum NEFA concentrations were measured using an enzymatic colorimetric method. Glomerular filtration rate (eGFR) was estimated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. RESULTS: Enrolled patients had a baseline mean eGFRCKD-EPI of 83 ± 12 mL/min/1.73 m2 and a median serum NEFA concentration of 662 uEq/L (interquartile range 524-842 uEq/L). During the follow-up period, 13 patients developed kidney function decline at follow-up (defined as an eGFRCKD-EPI decline ≥ 30% from baseline). In Cox proportional hazards regression analyses, higher serum NEFA levels were significantly associated with an increased risk of developing kidney function decline (adjusted-hazard ratio 3.67, 95% CI 1.64-8.22, p < 0.001; for each 1-SD increment, i.e., 262 uEq/L), even after adjustment for waist circumference, hemoglobin A1c, C-reactive protein, HOMA-estimated insulin resistance, hypertension, dyslipidemia, microalbuminuria, baseline eGFRCKD-EPI, as well as temporal changes in HbA1c levels or the use of renin-angiotensin system inhibitors over the follow-up. CONCLUSIONS: The findings of this exploratory prospective study show that in post-menopausal women with T2DM and preserved kidney function at baseline, higher circulating levels of NEFA were strongly associated with a faster kidney function decline, even after adjustment for established renal risk factors and potential confounders.

Cord Blood Metabolite Profiles and Their Association with Autistic Traits in Childhood.

Autism Spectrum Disorder (ASD) is a diverse neurodevelopmental condition. Gene-environmental interactions in early stages of life might alter metabolic pathways, possibly contributing to ASD pathophysiology. Metabolomics may serve as a tool to identify underlying metabolic mechanisms contributing to ASD phenotype and could help to unravel its complex etiology. In a population-based, prospective cohort study among 783 mother-child pairs, cord blood serum concentrations of amino acids, non-esterified fatty acids, phospholipids, and carnitines were obtained using liquid chromatography coupled with tandem mass spectrometry. Autistic traits were measured at the children's ages of 6 (n = 716) and 13 (n = 648) years using the parent-reported Social Responsiveness Scale. Lower cord blood concentrations of SM.C.39.2 and NEFA16:1/16:0 were associated with higher autistic traits among 6-year-old children, adjusted for sex and age at outcome. After more stringent adjustment for confounders, no significant associations of cord blood metabolites and autistic traits at ages 6 and 13 were detected. Differences in lipid metabolism (SM and NEFA) might be involved in ASD-related pathways and are worth further investigation.

Invited Review: Increasing Milk Yield and Negative Energy Balance: A Gordian Knot for Dairy Cows?

The continued increase in milk production during the last century has not been accompanied by an adequate dry matter intake (DMI) by cows, which therefore experience a negative energy balance (NEB). NEB is low and of minor importance at low milk yield (MY), such as for the nutrition of one calf, and under these circumstances is considered "natural". MY and low DMI around parturition are correlated and are the reason for the genetic correlation between increasing MY and increasing NEB up to 2000 MJ or more for 2-3 months postpartum in high-genetic-merit dairy cows. The extension and duration of NEB in high-producing cows cannot be judged as "natural" and are compensated by the mobilization of nutrients, particularly of fat. The released non-esterified fatty acids (NEFAs) overwhelm the metabolic capacity of the cow and lead to the ectopic deposition of NEFAs as triglycerides (TGs) in the liver. The subsequent lipidosis and the concomitant hampered liver functions cause subclinical and clinical ketosis, both of which are associated with "production diseases", including oxidative and endoplasmatic stress, inflammation and immunosuppression. These metabolic alterations are regulated by homeorhesis, with the priority of the physiological function of milk production. The prioritization of one function, namely, milk yield, possibly results in restrictions in other physiological (health) functions under conditions of limited resources (NEB). The hormonal framework for this metabolic environment is the high concentration of growth hormone (GH), the low concentration of insulin in connection with GH-dependent insulin resistance and the low concentration of IGF-1, the so-called GH-IGF-1 axis. The fine tuning of the GH-IGF-1 axis is uncoupled because the expression of the growth hormone receptor (GHR-1A) in the liver is reduced with increasing MY. The uncoupled GH-IGF-1 axis is a serious impairment for the GH-dependent stimulation of gluconeogenesis in the liver with continued increased lipolysis in fat tissue. It facilitates the pathogenesis of lipidosis with ketosis and, secondarily, "production diseases". Unfortunately, MY is still increasing at inadequate DMI with increasing NEB and elevated NEFA and beta-hydroxybutyric acid concentrations under conditions of low glucose, thereby adding health risks. The high incidences of diseases and of early culling and mortality in dairy cows are well documented and cause severe economic problems with a waste of resources and a challenge to the environment. Moreover, the growing public concerns about such production conditions in agriculture can no longer be ignored.

Adipose Tissue Protects against Hepatic Steatosis in Male Rats Fed a High-Fat Diet plus Liquid Fructose: Sex-Related Differences.

Non-alcoholic fatty liver disease is a sexual dimorphic disease, with adipose tissue playing an essential role. Our previous work showed that female rats fed a high-fat high-fructose diet devoid of cholesterol (HFHFr) developed simple hepatic steatosis dissociated from obesity. This study assessed the impact of the HFHFr diet on the male rat metabolism compared with data obtained for female rats. A total of 16 Sprague Dawley (SD) male rats were fed either a control (standard rodent chow and water) or HFHFr (high-fat diet devoid of cholesterol, plus 10% fructose in drinking water) diet for 3 months. Unlike female rats, and despite similar increases in energy consumption, HFHFr males showed increased adiposity and hyperleptinemia. The expression of hormone-sensitive lipase in the subcutaneous white adipose tissue was enhanced, leading to high free fatty acid and glycerol serum levels. HFHFr males presented hypertriglyceridemia, but not hepatic steatosis, partially due to enhanced liver PPARα-related fatty acid ß-oxidation and the VLDL-promoting effect of leptin. In conclusion, the SD rats showed a sex-related dimorphic response to the HFHFr diet. Contrary to previous results for HFHFr female rats, the male rats were able to expand the adipose tissue, increase fatty acid catabolism, or export it as VLDL, avoiding liver lipid deposition.

Essential Fatty Acid Deficiency Associates with Growth Faltering and Environmental Enteric Dysfunction in Children.

Environmental enteric dysfunction (EED) is characterized by intestinal inflammation, malabsorption and growth-faltering in children with heightened exposure to gut pathogens. The aim of this study was to characterize serum non-esterified fatty acids (NEFA), in association with childhood undernutrition and EED, as potential biomarkers to predict growth outcomes. The study comprised a cohort of undernourished rural Pakistani infants (n = 365) and age-matched controls followed prospectively up to 24 months of age. Serum NEFA were quantified at ages 3-6 and 9 months and correlated with growth outcomes, serum bile acids and EED histopathological biomarkers. Serum NEFA correlated with linear growth-faltering and systemic and gut biomarkers of EED. Undernourished children exhibited essential fatty acid deficiency (EFAD), with low levels of linoleic acid and total n-6 polyunsaturated fatty acids, compensated by increased levels of oleic acid and increased elongase and desaturase activities. EFAD correlated with reduced anthropometric Z scores at 3-6 and 9 months of age. Serum NEFA also correlated with elevated BA and liver dysfunction. Essential fatty acid depletion and altered NEFA metabolism were highly prevalent and associated with acute and chronic growth-faltering in EED. The finding suggests that targeting early interventions to correct EFAD and promote FA absorption in children with EED may facilitate childhood growth in high-risk settings.

L-carnitine enhances developmental potential of bovine oocytes matured under high lipid concentrations in vitro.

Maternal obesity elevates non-esterified fatty acids (NEFA) follicular concentrations. Bovine cumulus-oocyte complexes (COCs) matured in vitro under high NEFA have altered metabolism and reduced quality. Systemically, obesity promotes altered mitochondrial metabolism linked to L-carnitine insufficiency. We hypothesized that L-carnitine supplementation during IVM of bovine COCs in the presence of high NEFA would lessen the negative effects of exposure to excessive lipids on embryonic development and oxidative stress. COCs were collected from abattoir ovaries and matured in four groups: CON (control), LC (3 mM L-carnitine), HN (high NEFA: 200uM oleic, 150uM palmitic and 75uM stearic acid), and HNLC (HN and LC). Mature oocytes were assayed for aerobic and anaerobic metabolism utilizing oxygen and pH microsensors or fertilized in vitro (D0). Cleavage (D3) and blastocyst (D7, D8) rates were assessed. D3 embryos with ≥ 4 cells were stained for cytosolic and mitochondrial ROS. D8 blastocysts were assayed for gene transcript abundance of metabolic enzymes. Oocyte metabolism was not affected by IVM treatment. D3 formation of embryos with ≥ 4 cells were lower in LC or HN than CON or HNLC; blastocyst rates were greater for CON and lower for HN than LC and HNLC. D3 embryo mitochondrial and cytosolic ROS were reduced in HNLC when compared to other groups. IVM in HN altered blastocyst gene transcript abundance when compared to CON, but not LC or HNLC. In conclusion, supplementation with L-carnitine protects oocytes exposed to high NEFA during IVM and improves their developmental competence, suggesting that high lipid exposure may lead to L-carnitine insufficiency in bovine oocytes.

Non-esterified fatty acids and risk of peripheral artery disease in older adults: The cardiovascular health study.

BACKGROUND AND AIMS: Non-esterified fatty acids have been implicated in the pathogenesis of diabetes and cardiovascular disease. No longitudinal study has assessed their effects on peripheral artery disease (PAD). We determined the relationships between NEFAs and incident clinical PAD and abnormal ankle-brachial index (ABI) in a population-based cohort of older persons. METHODS: We evaluated 4575 community living participants aged >65 years who underwent measurement of circulating NEFAs in fasting specimens and ABI in 1992-1993. Participants were assessed annually for clinical PAD until 2015 and underwent repeat ABI in 1998-1999. We used Cox proportional hazards regression to model the associations between NEFAs and risk of clinical PAD and logistic regression to model the associations of NEFAs with incident abnormal ABI. RESULTS: Mean age was 74.8 years, 59% were female, and 17% were Black. NEFAs were associated with higher risk of clinical PAD in unadjusted and adjusted models. The adjusted hazard ratios for incident clinical PAD were 1.51 (95%CI = 1.06-2.13, p = 0.02) across extreme tertiles, and 1.14 (95%CI = 0.99-1.31, p = 0.08) per standard deviation higher NEFA. The corresponding odds ratios for abnormal ABI were 0.95 (95%CI = 0.69-1.32, p = 0.76) across extreme tertiles, and 1.03 (95%CI = 0.89-1.20, p = 0.68) per standard deviation higher NEFA. Relationships appeared similar irrespective of sex, race, or pre-existing cardiovascular disease, but were stronger later than earlier in follow-up. CONCLUSIONS: Higher serum levels of NEFAs are significantly associated with increased likelihood of clinical PAD over long-term follow-up but not with 6-year decline in ABI. NEFAs may offer a potential target for intervention against clinical PAD.

Influence of weaning management at 30, 75 and 180 days of age on non-esterified fatty acids and reproductive performance in beef cows.

This study aimed to investigate the effect of age at weaning of calves on non-esterified fatty acids (NEFA) and reproductive parameters of beef cows. Animals (n = 65) were randomly assigned to three treatments after calving: hyper-early weaning (W30) at 32 ± 0.89 days, early weaning (W75) at 77 ± 0.95 days, and conventional weaning (W180) at 183 ± 0.82 days. Body weight (BW) and body condition score (BCS) were evaluated at parturition (AP) and at 30, 45, 64, 81, 100 and 115 days postpartum (dPP). Blood samples were collected to analyze NEFA levels and progesterone (P4) at 30, 45, 64 and 81 dPP. Higher BW and BCS were observed from 64 to 115 dPP in W30 cows than W180 ones (p < 0.05). Cows subjected to W30 condition had higher levels of NEFA at 30 dPP compared to 64 and 81 dPP (p < 0.05). We also observed that cows from W180 group showed decreased levels of NEFA at 30 dPP compared to 45 (p < 0.01) and 64 dPP (p < 0.05). The highest P4 level was observed at 64 dPP in W30 cows compared to W75 and W180 (p < 0.05). We also observed higher CR of W30 (86%) compared to W180 (47%) at 45 dPP (p < 0.05). The overall pregnancy rate (PR) was higher for W30 (95.5%) than W180 (73.9%). In addition, higher BW at calving and P4 levels at 30 dPP were positively correlated with the possibility of pregnancy (p < 0.05). Improvement in BW and BCS were observed in cows subjected to hyper-early weaning management. However, levels of NEFA decreased as the postpartum period progressed. We concluded that cows who weaned calves hyper-early have greater chances of increasing cyclicity and PRs.

The impact of fasting on adipose tissue metabolism.

Fasting and starvation were common occurrences during human evolution and accordingly have been an important environmental factor shaping human energy metabolism. Humans can tolerate fasting reasonably well through adaptative and well-orchestrated time-dependent changes in energy metabolism. Key features of the adaptive response to fasting are the breakdown of liver glycogen and muscle protein to produce glucose for the brain, as well as the gradual depletion of the fat stores, resulting in the release of glycerol and fatty acids into the bloodstream and the production of ketone bodies in the liver. In this paper, an overview is presented of our current understanding of the effects of fasting on adipose tissue metabolism. Fasting leads to reduced uptake of circulating triacylglycerols by adipocytes through inhibition of the activity of the rate-limiting enzyme lipoprotein lipase. In addition, fasting stimulates the degradation of stored triacylglycerols by activating the key enzyme adipose triglyceride lipase. The mechanisms underlying these events are discussed, with a special interest in insights gained from studies on humans. Furthermore, an overview is presented of the effects of fasting on other metabolic pathways in the adipose tissue, including fatty acid synthesis, glucose uptake, glyceroneogenesis, autophagy, and the endocrine function of adipose tissue.

Fasting and Post-Load Glucose and Non-Esterified Fatty Acids and Risk of Heart Failure and Its Subtypes in Older Adults.

BACKGROUND: Glucose and non-esterified fatty acids (NEFA) are myocardial fuels whose fasting and post-prandial levels are under different homeostatic regulation. The relationships of fasting and post-load glucose and NEFA with incident heart failure (HF) remain incompletely defined. METHODS: Serum glucose and NEFA were measured during fasting and 2 hours post-oral glucose tolerance test, performed in Cardiovascular Health Study participants not receiving hypoglycemic medication. Participants with prevalent HF or lacking relevant data were excluded. Outcomes were incident HF (primary), and HF with preserved (HFpEF) and reduced (HFrEF) ejection fraction (secondary). RESULTS: Among 2 238 participants (age 78 ± 4) with a median follow-up of 9.9 years, there were 737 HF events. After adjustment for demographic and lifestyle factors, both fasting (hazard ratio [HR] = 1.11 per SD [95% confidence interval {CI} = 1.01-1.23], p = .040) and post-load (HR = 1.14 per SD [1.05-1.24], p = 0.002) glucose were significantly associated with incident HF. No association was seen for fasting or post-load NEFA. Upon mutual adjustment, only post-load glucose (HR = 1.11 [1.003-1.22], p = .044), but not fasting glucose (HR = 1.06 [0.94-1.20], p = .340), remained associated with HF. Further adjustment for cardiovascular disease and other risk factors in the causal pathway did not affect the association for post-load glucose, but eliminated that for fasting glucose. Associations for fasting and post-load glucose appeared stronger with higher adiposity and were observed specifically for HFrEF but not HFpEF. CONCLUSIONS: Fasting and post-load glucose, but not NEFA, were associated with incident HF. The association was especially robust for post-load glucose, suggesting that pathways involved in post-prandial dysglycemia could offer new targets for HF prevention late in life.

Collagen Remodeling and Fatty Acid Regulation Biomarkers in Understanding the Molecular Pathogenesis of Atrial Fibrillation.

INTRODUCTION: Atrial Fibrillation (AF) is the most common cardiac arrythmia in the world. Structural remodeling and fatty acid metabolism dysregulation are believed to play a role in the development of AF. This study explored different biomarkers in the blood of AF patients and a control population to determine if there was a significant difference between the two groups. MATERIAL AND METHODS: Plasma samples were collected from 73 patients with confirmed diagnosis of AF from Loyola University Clinic. Control group represented commercially available plasma (n = 50). Sandwich ELISA kits were used to quantify the collagen remodeling proteins and liver type fatty acid binding protein (L-FABP) in the AF population and the control population. Non-esterified fatty acids (NEFAs) were measured using an enzymatic colorimetric kit from Wako Diagnostics. Statistical analyses were performed using GraphPad Prism. RESULTS: All the collagen remodeling biomarkers were significantly higher in AF patients compared to the control group. The fatty acid dysregulation biomarkers were elevated in the AF patients. Spearman correlation analyses yielded significant correlations between L-FABP and TIMP-1 (r = 0.47, P < 0.001), NEFA and TIMP-2 (r = 0.41, P = 0.002), NEFA and ICTP (r = 0.41, P =0 .002), and NEFA and PIIINP (r = 0.61, P < 0.0001). SUMMARY AND CONCLUSIONS: The elevation of collagen remodeling biomarkers suggests an upregulation of these biomarkers and their potential role in AF, which may contribute to atrial fibrosis. L-FABP and NEFAs were elevated in AF patients. The correlations between the collagen remodeling and fatty acid dysregulation biomarkers may be due to their involvement in structural remodeling of the atria.

Associations of Early Pregnancy Metabolite Profiles with Gestational Blood Pressure Development.

Blood pressure development plays a major role in both the etiology and prediction of gestational hypertensive disorders. Metabolomics might serve as a tool to identify underlying metabolic mechanisms in the etiology of hypertension in pregnancy and lead to the identification of novel metabolites useful for the prediction of gestational hypertensive disorders. In a population-based, prospective cohort study among 803 pregnant women, liquid chromatography­mass spectrometry was used to determine serum concentrations of amino-acids, non-esterified fatty acids, phospholipids and carnitines in early pregnancy. Blood pressure was measured in each trimester of pregnancy. Information on gestational hypertensive disorders was obtained from medical records. Higher individual metabolite concentrations of the diacyl-phosphatidylcholines and acyl-lysophosphatidylcholines group were associated with higher systolic blood pressure throughout pregnancy (Federal Discovery Rate (FDR)-adjusted p-values < 0.05). Higher concentrations of one non-esterified fatty acid were associated with higher diastolic blood pressure throughout pregnancy (FDR-adjusted p-value < 0.05). Using penalized regression, we identified 12 individual early-pregnancy amino-acids, non-esterified fatty acids, diacyl-phosphatidylcholines and acyl-carnitines and the glutamine/glutamic acid ratio, that were jointly associated with larger changes in systolic and diastolic blood pressure from first to third trimester. These metabolites did not improve the prediction of gestational hypertensive disorders in addition to clinical markers. In conclusion, altered early pregnancy serum metabolite profiles mainly characterized by changes in non-esterified fatty acids and phospholipids metabolites are associated with higher gestational blood pressure throughout pregnancy within the physiological ranges. These findings are important from an etiological perspective and, after further replication, might improve the early identification of women at increased risk of gestational hypertensive disorders.