GLUT4 localisation with the plasma membrane is unaffected by an increase in plasma free fatty acid availability.

BACKGROUND: Insulin-stimulated glucose uptake into skeletal muscle occurs via translocation of GLUT4 from intracellular storage vesicles to the plasma membrane. Elevated free fatty acid (FFA) availability via a lipid infusion reduces glucose disposal, but this occurs in the absence of impaired proximal insulin signalling. Whether GLUT4 localisation to the plasma membrane is subsequently affected by elevated FFA availability is not known. METHODS: Trained (n = 11) and sedentary (n = 10) individuals, matched for age, sex and body mass index, received either a 6 h lipid or glycerol infusion in the setting of a concurrent hyperinsulinaemic-euglycaemic clamp. Sequential muscle biopsies (0, 2 and 6 h) were analysed for GLUT4 membrane localisation and microvesicle size and distribution using immunofluorescence microscopy. RESULTS: At baseline, trained individuals had more small GLUT4 spots at the plasma membrane, whereas sedentary individuals had larger GLUT4 spots. GLUT4 localisation with the plasma membrane increased at 2 h (P = 0.04) of the hyperinsulinemic-euglycemic clamp, and remained elevated until 6 h, with no differences between groups or infusion type. The number of GLUT4 spots was unchanged at 2 h of infusion. However, from 2 to 6 h there was a decrease in the number of small GLUT4 spots at the plasma membrane (P = 0.047), with no differences between groups or infusion type. CONCLUSION: GLUT4 localisation with the plasma membrane increases during a hyperinsulinemic-euglycemic clamp, but this is not altered by elevated FFA availability. GLUT4 appears to disperse from small GLUT4 clusters located at the plasma membrane to support glucose uptake during a hyperinsulinaemic-euglycaemic clamp.

Effects of Individual Circulating FFAs on Plasma and Hepatic FFA Epoxides, Diols, and Epoxide-Diol Ratios as Indices of Soluble Epoxide Hydrolase Activity.

Oxylipins, oxidation products of unsaturated free fatty acids (FFAs), are involved in various cellular signaling systems. Among these oxylipins, FFA epoxides are associated with beneficial effects in metabolic and cardiovascular health. FFA epoxides are metabolized to diols, which are usually biologically less active, by soluble epoxide hydrolase (sEH). Plasma epoxide-diol ratios have been used as indirect measures of sEH activity. This study was designed to examine the effects of acute elevation of individual plasma FFAs on a variety of oxylipins, particularly epoxides, diols, and their ratios. We tested if FFA epoxide-diol ratios are altered by circulating FFA levels (i.e., substrate availability) independent of sEH activity. Wistar rats received a constant intravenous infusion of olive (70% oleic acid (OA)), safflower seed (72% linoleic acid (LA)), and fish oils (rich in ω-3 FFAs) as emulsions to selectively raise OA, LA, and ω-3 FFAs (eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)), respectively. As expected, olive, safflower seed, and fish oil infusions selectively raised plasma OA (57%), LA (87%), EPA (70%), and DHA (54%), respectively (p < 0.05 for all). Raising plasma FFAs exerted substrate effects to increase hepatic and plasma epoxide and diol levels. These increases in epoxides and diols occurred to similar extents, resulting in no significant changes in epoxide-diol ratios. These data suggest that epoxide-diol ratios, often used as indices of sEH activity, are not affected by substrate availability or altered plasma FFA levels and that epoxide-diol ratios may be used to compare sEH activity between conditions of different circulating FFA levels.

Cardiac arrest due to a fatal dose of propranolol successfully treated with intravenous lipid infusion.

BACKGROUND: Beta blockers (BB) are used for very different indications in both adults and children. There can be mild adverse effects with normal doses. When taken in toxic doses, this can have fatal results in children. There are some standard therapies during BB poisoning such as insulin and glucagon but there is not enough knowledge concerning intravenous lipid infusion therapy (ILI). CASE: Herein we present a case of propranolol poisoning in a previously healthy 2-year-old girl. In this patient, cardiac arrest developed twice, and cardiopulmonary resuscitation was performed for 5 and 20 minutes, respectively. We initiated inotropes, insulin, calcium and glucagon with a lack of response to all medical treatment. We used ILI and the patient improved after this treatment. She recovered without any disability. CONCLUSIONS: ILI treatment should be considered with life-threatening BB poisoning which is unresponsive to standard therapies.

Intravenous lipid infusion affects dry matter intake, methane yield, and rumen bacteria structure in late-lactating Holstein cows.

Increasing the dietary fat content of ruminant diets decreases methane (CH4) production. This effect is caused by the toxic properties of fatty acids on rumen microbial populations, coating of feed particles diminishing the accessibility for microbes, and a reduction in dry matter intake (DMI). The latter effect is caused by postabsorptive long-chain fatty acids eliciting anorexic signaling; however, whether circulating long-chain fatty acids affect rumen CH4 production alike is unknown. To approach this question, 5 rumen-cannulated Holstein cows in late lactation received 2 jugular catheters and were kept in respiration chambers to measure CH4 production and DMI for 48 h. In a crossover design, cows were intravenously infused with a 20% lipid emulsion (LIPO) or 0.9% NaCl (CON). The LIPO cows received 2.1 kg of triglycerides/d [0.152 ± 0.007 g of triglycerides/(kg of BW × h)-1] consisting of 12.1% palmitic acid, 4.2% stearic acid, 31.1% oleic acid, and 52.7% linoleic acid. Blood and rumen fluid samples were taken hourly during the day. Results showed that LIPO compared with CON infusion increased plasma triglyceride as well as free fatty acid and serotonin concentrations but reduced the proportion of de novo synthesized milk fatty acids (sum of C6 to C16). Daily CH4 production and DMI were lower, whereas daily CH4 yield (CH4/DMI) was greater in LIPO than CON cows, although CH4 yield decreased from d 1 to d 2 by 2 to 14% in LIPO-infused cows only. This effect was associated with a higher (acetate + butyrate)/propionate ratio, tending lower propionate concentrations between 24 and 34 h of infusion, reduced relative abundances of genera belonging to Succinivibrio, Ruminococcaceae, and Ruminiclostridium, and greater relative Bacteroidetes genus abundances in the rumen.

Association of intralipid intake in extremely low birthweight infants with neurodevelopmental outcomes.

AIM: To determine whether high intake of intralipid (IL) in extremely low birthweight (ELBW) neonates is associated with higher rates of neuroimpairment and Bayley III scores at two years of corrected age. METHODS: Quartiles of IL received by 389 ELBW infants were linked to neurodevelopmental outcomes. Logistic regression analyses, adjusted for confounders, were performed to determine the association between IL dose and neuroimpairment. Linear regression analyses were performed to predict Bayley III scores. RESULTS: No association was found between IL dose and neuroimpairment A significant association was found between higher IL intake and lower Bayley Cognitive, motor and language scores. Adding breast milk intake to the linear regression eliminated the associations. CONCLUSION: Higher IL intake was associated with lower cognitive, motor and language scores. Breast milk intake eliminated the latter associations, which underscores the important role of breast milk in developmental outcome.

Pre-Pregnancy Levels of Peripheral Natural Killer Cells as Markers for Immunomodulatory Treatment in Patients with Recurrent Miscarriage.

Immunological risk factors in patients with recurrent miscarriage (RM) are discussed controversially. Abnormalities of natural killer cells (NK) have been described in RM patients. Lipid infusions are known to modulate lymphocyte subsets. The aim of this study was to identify immune parameters that predict success of treatment with lipid infusions in RM patients with elevated NK. In sum, n = 341 couples with RM were screened for established risk factors and peripheral lymphocyte subpopulations as well as uterine NK cells. We identified n = 136 patients with ≥ 2 consecutive RM and elevated NK. So far, n = 40 RM patients with NK disorders were treated with lipid infusions starting at positive pregnancy test, every 2 weeks until 12 + 0 weeks of gestation (GW) or miscarriage. The pre-pregnancy immune diagnostics in idiopathic RM (iRM) patients with ongoing pregnancy were compared to the group with miscarriages and healthy controls (n = 15). Pre-pregnancy immune diagnostics differed significantly between the groups, with significant higher levels of peripheral NK (% and /µL) in iRM patients who miscarried again compared to controls (p = 0.0035 and p = 0.0019). Furthermore, iRM patients show lower percentages of CD3+ lymphocytes than healthy controls (p = 0.0049). In n = 22/40 (55%) patients, pregnancy is ongoing >12 + 0 GW. RM patients with very high pre-pregnancy peripheral NK (pNK) lymphocytes might not benefit from lipid infusions. Pre-pregnancy immunomodulatory treatment in RM patients might be helpful to lower pNK levels and establish an immune environment which is supportive for fetal development.

Acute severe organophosphate poisoning in a child who was successfully treated with therapeutic plasma exchange, high-volume hemodiafiltration, and lipid infusion.

Acute severe organophosphate poisoning is a serious complication seen in developing and agricultural countries. Pralidoxime and high dose atropine are the standard treatments. There is no consensus about acute severe organophosphate poisonings that are unresponsive to pralidoxime, atropine, and supportive therapies. We report a case of acute severe organophosphate poisoning that was unresponsive to standard treatments and successfully treated with high-volume continuous venovenous hemodiafiltration and therapeutic plasma exchange combined with lipid infusion. J. Clin. Apheresis 31:467-469, 2016. © 2015 Wiley Periodicals, Inc.