-
1.
Regulation of direct adipose tissue free fatty acid storage during mixed meal ingestion and high free fatty acid concentration conditions.
Zhang, L, Hames, KC, Jensen, MD
American journal of physiology. Endocrinology and metabolism. 2021;(2):E208-E218
Abstract
We found that direct free fatty acid (FFA) storage (fatty acid cycling back into adipose tissue) in leg vs. abdominal subcutaneous fat is related to regional differences in adipose tissue diacylglycerol acyltransferase (DGAT) activity under high-FFA conditions and to differences in adipose tissue acyl-CoA synthetase (ACS)activity under meal ingestion conditions. We also found that direct FFA storage rates in leg fat were significantly less in physically active than sedentary adults. Direct FFA storage into adipocytes relates to body fat distribution. Adipose tissue CD36, ACS, and DGAT may account for some of the between-depot and interindividual variability in FFA storage. These studies were to test whether CD36, ACS, or DGAT might be important for direct palmitate storage under meal ingestion or high-FFA conditions. We measured upper (UBSQ) and lower body subcutaneous (LBSQ) adipose tissue FFA storage rates by infusing palmitate tracers intravenously and performing adipose biopsies under hypoinsulinemic (high-FFA) and mixed-meal conditions. We recruited five postmenopausal women, physically active males (5) and females (5), and sedentary males (5) and females (5). We found that 1) the ratio of UBSQ to LBSQ DGAT activity predicted the ratio of palmitate storage [adjusted R = 0.25, F = 8.0, P = 0.01, 95% CI (0.07, 0.48)] under high-FFA conditions; 2) the ratio of UBSQ to LBSQ ACS activity predicted the ratio of palmitate storage under meal conditions [adjusted R = 0.18, F = 6.3, P = 0.02, 95% CI (0.12, 1.28)]; 3) LBSQ direct palmitate storage rates were significantly less in physically active than sedentary and 4) adipose tissue CD36 protein content, ACS, or DGAT activities did not independently predict palmitate storage rates. We conclude that physically active adults have lesser fatty acid cycling back into adipose tissue and that adipose ACS and DGAT may affect competition between UBSQ and LBSQ adipose for direct palmitate storage.
-
2.
The Association of Free Fatty Acids and Eicosanoids with the Severity of Depressive Symptoms in Stroke Patients.
Kotlega, D, Zembron-Lacny, A, Golab-Janowska, M, Nowacki, P, Szczuko, M
International journal of molecular sciences. 2020;(15)
Abstract
The study was designed to demonstrate the relationship of free fatty acids (FFAs) and eicosanoids levels with the severity of depressive symptoms in stroke. The ischemic stroke patients (n = 74) were included in the prospective study. The risk of depression was evaluated by the Beck Depression Inventory-II (BDI-II) 7 days and 6 months after the stroke onset. FFAs and inflammatory metabolites were determined by gas chromatography and liquid chromatography. In the acute phase of stroke, BDI-II and FFAs inversely correlated with C13:0 tridecanoic acid, C15:1 cis-10-pentadecanoid acid, C17:1 cis-10- heptadecanoid acid, C18:0 stearic acid, C20:3n6 eicosatrienoic acid, C22:1cis13 docosenoic acid and C22:6n3 docosahexaenoic acid (DHA). DHA level was significantly lower in patients with low vs. high BDI-II score. In the follow-up examination, BDI-II score directly correlated with C16:0 palmitic acid. The changes in BDI-II score during 6-month observation inversely correlated with lipoxin A4 and protectin D1, and directly correlated with 5-oxo-ETE. Importantly, the severity of depressive symptoms was associated with n3 PUFA level. Diet-derived FFAs were observed to potentially affect the inflammatory pathways in pathogenesis of depression in stroke and reduced DHA levels can attenuate depressive symptoms in stroke patients.
-
3.
Effects of soybean lipid infusion on triglyceride and unbound free fatty acid levels in preterm infants.
Hegyi, T, Kleinfeld, A, Huber, A, Weinberger, B, Memon, N, Joe Shih, W, Carayannopoulos, M, Oh, W
The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians. 2019;(19):3226-3231
-
-
Free full text
-
Abstract
Objective: To determine the plasma triglyceride (TG) and unbound free fatty acid (FFAu) levels in infants treated with increasing dosages of soybean lipid, intralipid (IL), infusion. Study design: TG and FFAu levels were measured in 78 preterm infants (BW 500-2000 g; GA 23-34 weeks) using the fluorescent probe ADIFAB2 and enzymatic method. Results: The infants' BW was 1266.2 ± 440.7 g and GA 28.8 ± 3.1 weeks. TG levels were 77.4 ± 50 mg/dL, 140.2 ± 188 mg/dL (p < .04 compared to levels during low dose IL infusion) and 135.6 ± 118 mg/dL (p < .004), respectively during increased IL rates. FFAu levels were 17.7 ± 13 nM, 47.3 ± 102.8 nM (p = .07) and 98 ± 234 nM (p = .03). TG levels correlated with IL dose, the rate of IL administration, and FFAu levels. TG and FFAu levels were higher in infants below 28 weeks' gestation Conclusions: Increasing dosage of IL is associated with increasing levels of TG and FFAu, especially in infants below 29 weeks of gestation. The increased level of FFAu suggests inefficient cellular utilization.
-
4.
A pilot study of the effects of niacin administration on free fatty acid and growth hormone concentrations in children with obesity.
Galescu, OA, Crocker, MK, Altschul, AM, Marwitz, SE, Brady, SM, Yanovski, JA
Pediatric obesity. 2018;(1):30-37
-
-
Free full text
-
Abstract
CONTEXT Children with obesity have low spontaneous growth hormone (GH) secretion. High circulating free fatty acid (FFA) concentration is believed to inhibit GH secretion in those with obesity. In adults, lipolytic inhibition with niacin lowers FFA and increases GH, but there are no prior studies in children with obesity. OBJECTIVE The objective of the study was to determine the dose and frequency of niacin administration required to lower FFA and stimulate GH in children with obesity. DESIGN Dose-finding study of nondiabetic children ages 6-12 years with body mass index (BMI) ≥ 95th percentile given niacin 250 mg q2h × 3 doses (n = 2), 500 mg q2h × 3 doses (n = 5) or 500 mg q1h × 4 doses (n = 5). PARTICIPANTS Eight boys and four girls (age 9.7 ± 1.8 years; BMI 26.4 ± 3.1 kg m-2 ; BMIz 2.2 ± .25) were studied. MAIN OUTCOME Percentage of serum FFA values that were below 0.2 mEq L-1 . GH, insulin and glucose were also measured serially. RESULTS FFA decreased as the dose and frequency of niacin increased (p = .01). Niacin 500 mg q1h 4 doses suppressed FFA < 0.2 mEq L-1 and significantly increased GH (p = .04). Adverse effects were flushing/warmth (100%), tingling (60%) and GI complaints (20-40%). CONCLUSIONS Niacin 500 mg q1h significantly lowered serum FFA and increased GH. These pilot data suggest that high FFA is an important suppressor of GH secretion in children with obesity.
-
5.
The role of free fatty acids in the inflammatory and cardiometabolic profile in adolescents with metabolic syndrome engaged in interdisciplinary therapy.
Masquio, DC, de Piano-Ganen, A, Oyama, LM, Campos, RM, Santamarina, AB, de Souza, GI, Gomes, AD, Moreira, RG, Corgosinho, FC, do Nascimento, CM, et al
The Journal of nutritional biochemistry. 2016;:136-44
Abstract
The purpose of the present study was to evaluate if interdisciplinary therapy can influence the cardiometabolic and serum free fatty acid profile. The second aim was to evaluate if there is an association between serum free fatty acids, inflammation and cardiometabolic biomarkers in obese adolescents with and without metabolic syndrome submitted to a long-term interdisciplinary therapy. The study involved 108 postpuberty obese adolescents, who were divided according to metabolic syndrome (MetS) diagnosis: MetS (n=32) and Non-MetS (n=76). The interdisciplinary therapy consisted of a 1-year period of nutrition, psychology, physical exercise and clinical support. After therapy, both groups improved metabolic, inflammatory (leptin, adiponectin, leptin/adiponectin ratio, adiponectin/leptin ratio and C-reactive protein) and cardiometabolic profile (PAI-1 and ICAM). Metabolic syndrome prevalence reduced from 28.70% to 12.96%. Both groups reduced myristic acid (C14:0) and increased docosahexaenoic acid (DHA, C22:6n3), heneicosapentaenoic acid (HPA, C21:5n3) and arachidonic acid (C20:4n6). After adjustment for metabolic syndrome and the number of metabolic syndrome parameters, multiple regression analysis showed that changes in VCAM and PAI-1 were negatively associated with changes in cis-linoleic acid (C18:2n6c). Additionally, changes in trans-linoleic acid (C18:2n6t) were also positively associated with these biomarkers. Moreover, leptin and leptin/adiponectin ratio were negatively associated with changes in docosapentaenoic acid (DPA, C22:5n3) and stearidonic acid (SDA, C18:4n3). Adiponectin/leptin ratio was positively associated with docosapentaenoic acid (DPA, C22:5n3). Changes in adiponectin were positively correlated with changes in omega 3, such as heneicosapentaenoic acid (HPA, C21:5n3) and docosapentaenoic acid (DPA, C22:5n3). Results support that interdisciplinary therapy can control inflammatory and cardiometabolic profile in obese adolescents. Moreover, serum fatty acids can be influenced by lifestyle changes and are able to modulate these biomarkers.
-
6.
Does 8 weeks of strenuous bicycle exercise improve diabetes-related inflammatory cytokines and free fatty acids in type 2 diabetes patients and individuals at high-risk of metabolic syndrome?
Madsen, SM, Thorup, AC, Bjerre, M, Jeppesen, PB
Archives of physiology and biochemistry. 2015;(4):129-38
Abstract
UNLABELLED In the present study, the effects of 8 weeks of low volume high intensity interval training (HIIT) was investigated on circulating diabetes-related cytokines and free fatty acids (FFA) in adults with type 2 diabetes (T2D) and matched controls (CON). METHODS Participants exercised for 8 weeks (3 weekly sessions: 10 × 60 sec HIIT) on a cycle ergometer supervised by medical staff. Prior to the intervention and after the last HIIT session, venous blood samples were collected. RESULTS Circulating omentin-1 concentrations increased significantly in both the CON-group (p = 0.003) and in the T2D-group (p = 0.002). Pentraxin-3 (p = 0.010) and IL-1ra (p = 0.031) levels increased significantly in the CON-group. Plasma FFA in the T2D-group was significantly reduced after 60 min (p = 0.011). Post HIIT area under curve of circulating FFAs was reduced by -17.73 ± 6.99% (p = 0.041) in the T2D-group. CONCLUSION We observed only modest exercise-induced improvements of multiple diabetes-related cytokines. Circulating levels of FFAs were significantly lowered in the T2D-group.
-
7.
Effects of weight loss via high fat vs. low fat alternate day fasting diets on free fatty acid profiles.
Varady, KA, Dam, VT, Klempel, MC, Horne, M, Cruz, R, Kroeger, CM, Santosa, S
Scientific reports. 2015;:7561
Abstract
Cardiovascular disease risk is associated with excess body weight and elevated plasma free fatty acid (FFA) concentrations. This study examines how an alternate-day fasting (ADF) diet high (HF) or low (LF) in fat affects plasma FFA profiles in the context of weight loss, and changes in body composition and lipid profiles. After a 2-week weight maintenance period, 29 women (BMI 30-39.9 kg/m(2)) 25-65 years old were randomized to an 8-week ADF-HF (45% fat) diet or an ADF-LF (25% fat) diet with 25% energy intake on fast days and ad libitum intake on feed days. Body weight, BMI and waist circumference were assessed weekly and body composition was measured using dual x-ray absorptiometry (DXA). Total and individual FFA and plasma lipid concentrations were measured before and after weight loss. Body weight, BMI, fat mass, total cholesterol, LDL-C and triglyceride concentrations decreased (P < 0.05) in both groups. Total FFA concentrations also decreased (P < 0.001). In the ADF-LF group, decreases were found in several more FFAs than in the ADF-HF group. In the ADF-HF group, FFA concentrations were positively correlated with waist circumference. Depending on the macronutrient composition of a diet, weight loss with an ADF diet decreases FFA concentrations through potentially different mechanisms.
-
8.
One-week high-fat diet leads to reduced toll-like receptor 2 expression and function in young healthy men.
Wan, Z, Durrer, C, Mah, D, Simtchouk, S, Little, JP
Nutrition research (New York, N.Y.). 2014;(12):1045-51
Abstract
Toll-like receptor 2 (TLR2) is implicated in inflammatory responses to high-fat diet (HFD)-induced obesity in rodents, but human HFD studies examining TLR2-mediated immune responses are lacking. Our aim was to determine whether HFD affected TLR2 function in humans. We hypothesized that a short-term HFD in humans would impair TLR2-mediated immune function. Fasting blood samples were obtained from healthy young men (N = 9) before and after a 7-day HFD. Toll-like receptor 2 function was assessed in ex vivo whole blood cultures stimulated with the TLR2 agonist N-palmitoyl-S-[2,3-bis[palmitoyloxy]-[2RS]-propyl]-[R]-cysteinyl-[S]-seryl-[S]-lysyl-[S]-lysyl-[S]-lysyl-[S]-lysine (Pam3-Cys-SK4). Peripheral blood mononuclear cells (PBMCs) were isolated to examine TLR2, TLR4, and p47 subunit of nicotinamide adenine dinucleotide phosphate oxidase (p47(phox)) protein expression via Western blotting. Pam3-Cys-SK4-stimulated secretion of interleukin-1β (-35%, P = .005), interleukin-6 (-32%, P = .01), and tumor necrosis factor-α (-33%, P = .06) was reduced following the HFD. High-fat diet resulted in decreased TLR2 (P = .049) and p47(phox) (P = .037) protein expression from PBMCs. To mimic lipid overload ex vivo, follow-up experiments were performed in whole blood cultures exposed to a mixture of free fatty acids for 24 hours; and surface protein expression of TLR2 and TLR4 on CD14+ monocytes was measured by flow cytometry. Free fatty acid exposure for 24 hours ex vivo reduced monocyte TLR2 levels by about 20% (P = .028). A 7-day HFD in young healthy men resulted in impaired TLR2 function. Decreased TLR2 and p47(phox) protein expression in PBMCs, possibly due to excess free fatty acids, may mediate this response. Our current findings indicate that impaired TLR2 response after HFD might be partially responsible for increased risk of infection in diet-induced obesity.
-
9.
Postprandial glucose, insulin, and free fatty acid responses to sucrose consumed with blackcurrants and lingonberries in healthy women.
Törrönen, R, Kolehmainen, M, Sarkkinen, E, Mykkänen, H, Niskanen, L
The American journal of clinical nutrition. 2012;(3):527-33
-
-
Free full text
-
Abstract
BACKGROUND Sucrose induces high postprandial glucose and insulin responses. In vitro studies suggest that berries may reduce the digestion and absorption of sucrose and thereby suppress postprandial glycemia, but the evidence in humans is limited. OBJECTIVE We investigated the effects of sucrose ingested with blackcurrants (Ribes nigrum) and lingonberries (Vaccinium vitis-idaea) on postprandial glucose, insulin, and free fatty acid responses. DESIGN Twenty healthy women participated in a randomized, controlled, crossover meal study. They consumed whole blackcurrants or lingonberries (150 g served as purées) or blackcurrant or lingonberry nectars (300 mL), each with 35 g added sucrose. Sucrose alone (35 g in 300 mL water) was used as a reference. Blood samples were collected at 0, 15, 30, 45, 60, 90, and 120 min. RESULTS In comparison with sucrose alone, ingestion of sucrose with whole berries resulted in reduced glucose and insulin concentrations during the first 30 min and a slower decline during the second hour and a significantly improved glycemic profile. Berries prevented the sucrose-induced late postprandial hypoglycemic response and the compensatory free fatty acid rebound. Nearly similar effects were observed when sucrose was consumed with berry nectars. The improved responses were evident despite the higher content of available carbohydrate in the berry and nectar meals, because of the natural sugars present in berries. CONCLUSIONS Blackcurrants and lingonberries, as either whole berries or nectars, optimize the postprandial metabolic responses to sucrose. The responses are consistent with delayed digestion of sucrose and consequent slower absorption of glucose.
-
10.
Young women partition fatty acids towards ketone body production rather than VLDL-TAG synthesis, compared with young men.
Marinou, K, Adiels, M, Hodson, L, Frayn, KN, Karpe, F, Fielding, BA
The British journal of nutrition. 2011;(6):857-65
-
-
Free full text
-
Abstract
Before the menopause, women are relatively protected against CVD compared with men. The reasons for this sex difference are not completely understood, but hepatic fatty acid metabolism may play a role. The present study aimed to investigate the utilisation of plasma NEFA by the liver and to determine whether they are partitioned differently into ketone bodies and VLDL-TAG in healthy, lean young men and women. Volunteers were studied during a prolonged overnight fast (12-19 h) using an intravenous infusion of [U-¹³C]palmitate. After 12 h fasting, the women had a more advantageous metabolic profile with lower plasma glucose (P < 0·05) and TAG (P < 0·05) but higher plasma NEFA (P < 0·05) concentrations. Plasma 3-hydroxybutyrate (3-OHB) concentrations rose more in women than in men, and the transfer of ¹³C from [U-¹³C]palmitate to plasma [¹³C]3-OHB reached a plateau 6-7 h after the start of the infusion in women but was still increasing at 6 h in men. This implies a slower 3-OHB production rate and/or dilution by other precursor pools in men. In women, the high isotopic enrichment of plasma 3-OHB suggested that systemic plasma fatty acids were the major source of 3-OHB production. However, in men, this was not observed during the course of the study (P < 0·01). There were no sex differences for the incorporation of ¹³C into VLDL1- or VLDL2-TAG. The ability of young women to partition fatty acids towards ketone body production rather than VLDL-TAG may contribute to their more advantageous metabolic profile compared with young men.