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A high dose of whey protein hydrolysate fed with milk minerals rich in calcium (Capolac®) results in enhanced glucagon-like peptide-1 (GLP-1) concentrations in lean individuals; however, the effect of different calcium doses ingested alongside protein is unknown. The present study assessed the dose response of calcium fed alongside 25 g whey protein hydrolysate on GLP-1 concentrations in individuals with overweight/obesity. Eighteen adults (mean ± sd: 8M/10F, 34 ± 18 years, 28·2 ± 2·9 kgm−2) completed four trials in a randomised, double-blind, crossover design. Participants consumed test solutions consisting of 25 g whey protein hydrolysate (CON), supplemented with 3179 mg (LOW), 6363 mg (MED) or 9547 mg (HIGH) Capolac® on different occasions, separated by at least 48 h. The calcium content of test solutions equated to 65, 892, 1719 and 2547 mg, respectively. Arterialised-venous blood was sampled over 180 min to determine plasma concentrations of GLP-1TOTAL, GLP-17–36amide, insulin, glucose, NEFA, and serum concentrations of calcium and albumin. Ad libitum energy intake was measured at 180 min. Time–averaged incremental AUC (iAUC) for GLP-1TOTAL (pmol·l−1·min−1) did not differ between CON (23 ± 4), LOW (25 ± 6), MED (24 ± 5) and HIGH (24 ± 6). Energy intake (kcal) did not differ between CON (940 ± 387), LOW (884 ± 345), MED (920 ± 334) and HIGH (973 ± 390). Co-ingestion of whey protein hydrolysate with Capolac® does not potentiate GLP-1 release in comparison with whey protein hydrolysate alone. The study was registered at clinical trials (NCT03819972). [ABSTRACT FROM AUTHOR]

Modulation of cytosolic phospholipase A2 (cPLA2) activity by sphingomyelin (SPH), ceramide (Cer), and cholesterol (Chol) was investigated in CHO-2B cells activated by the calcium ionophore A23187 and epinephrine. Chol depletion of CHO-2B cells by treatment with methyl-β-cyclodextrin (5 mm) resulted in the inhibition of the release of arachidonic acid whereas the restoration of the level by Chol-loaded cyclodextrin relieved inhibition. Conversion of CHO-2B cellular SPH to Cer by Staphylococcus aureus sphingomyelinase enhanced endogenous cPLA2 activation as well as uptake by cells of C2- and C6-ceramide analogs. These results were confirmed in vitro with purified human recombinant cPLA2 acting on a model phospholipid substrate. The enzyme activity was inhibited by SPH but reactivated by Cer as well as by Chol added to glycerophospholipid liposomal substrates containing SPH. The results of this study, which combine in situ and in vitro experimental approaches, indicate that membrane microdomains enriched in SPH and Chol play a role in the modulation of the activity of cPLA2 and in arachidonic acid-derived mediator production.—Klapisz, E., J. Masliah, G. Béréziat, C. Wolf, and K. S. Koumanov. Sphingolipids and cholesterol modulate membrane susceptibility to cytosolic phospholipase A2. J. Lipid Res. 2000. 41: 1680–1688.

In the Arbuckle area of the Sacramento Valley, a 22-acre orchard was planted in 1990 with four almond varieties (‘Nonpareil’, ‘Butte’, ‘Carmel’ and ‘Monterey’). The orchard was irrigated with three types of microirrigation — surface drip, subsurface drip and microsprinklers. The orchard soils are 3 to 4 feet of gravelly, loamy sand overlaying a restricting clay layer. The coarse-textured soil with its low water-holding capacity allows little lateral movement of water from the microirrigation emission device. Under these soil conditions, microsprinkler-irrigated trees produced larger almond yields and showed greater tree growth. In addition, irrigation system evaluations show that all three microirrigation systems provide excellent irrigation uniformity levels after 8 years of operation with only routine maintenance.

In insulin target tissues, GLUT4 is known to traffic through multiple compartments that may involve ubiquitin- and/or SUMO-dependent targeting. During these trafficking steps, GLUT4 is sorted into a storage reservoir compartment that is acutely released by insulin signalling processes that are downstream of PI 3-kinase associated changes in inositol phospholipids. As ESCRT components have recently been found to influence cellular sorting processes that are related to changes in both ubiquitination and inositol phospholipids, we have examined whether GLUT4 traffic is routed through ESCRT dependent sorting steps. Introduction of the dominant negative inhibitory constructs of the ESCRT-III components CHMP3 (CHMP3(1-179)) and Vps4 (GFP-Vps4(E235Q)) into rat adipocytes leads to the accumulation of GLUT4 in large, coalesced and extended vesicles structures that co-localise with the inhibitory constructs over large parts of the extended structure. A new swollen hybrid and extensively ubiquitinated compartment is produced in which GLUT4 co-localises more extensively with the endosomal markers including EEA1 and transferrin receptors but also with the TGN marker syntaxin6. These perturbations are associated with failure of insulin action on GLUT4 traffic to the cell surface and suggest impairment in an ESCRT-dependent sorting step used for GLUT4 traffic to its specialised reservoir compartment.

Fructose-containing sugars can exaggerate postprandial lipaemia and stimulate hepatic de novo lipogenesis (DNL) when compared to glucose-based carbohydrates(1). Galactose has recently been shown to increase postprandial lipaemia compared to glucose(2), but mechanisms remain uncharacterised. The aim of this study was to assess the effect and mechanisms of lactose-induced lipaemia. Twenty-four non-obese adults (12 male and 12 female) completed three trials in a randomised, crossover design (28 ± 7-day washout). During trials, participants consumed test drinks containing 50 g fat with 100 g of carbohydrate. The control carbohydrate was a glucose polymer (maltodextrin), the experimental carbohydrate was galactose-containing carbohydrate (lactose) and the active comparator was fructose-containing carbohydrate (sucrose). Hepatic DNL was assessed by the 2H2O method and [U-13C]-palmitate was added to the test drink to trace the fate of the ingested fat. Blood and breath samples were taken to determine plasma metabolite and hormone concentrations, in addition to plasma and breath 2H and 13C enrichments. Data were converted into incremental under the curve (iAUC) and were checked for normality by visual inspection of residuals. Differences between trials were assessed by one-way ANOVA. Where a main effect of trial was detected, post- hoc t-tests were performed to determine which trials differed from lactose according to the principle of closed-loop testing. The plasma triacylglycerol iAUC (mean ± SD) in response to maltodextrin was 51 ± 68 mmol/L*360 min. Following lactose ingestion, plasma triacylglycerol iAUC increased to 98 ± 88 mmol/L*360 min (p<0.001 vs maltodextrin), which was comparable to sucrose [90 ± 95 mmol/L*360 min (p=0.41 vs lactose)]. Hepatic DNL in response to maltodextrin was 6.6 ± 3.0%. Following ingestion of lactose, hepatic DNL increased to 12.4 ± 6.9% (p=0.02 vs maltodextrin), which was comparable to sucrose [12.2 ± 6.9% (p=0.96 vs lactose)]. Exhaled 13CO2 in response to maltodextrin was 10.4 ± 4.1 mmol/kgFFM*360 min. Following ingestion of lactose, exhaled 13CO2 was 8.8 ± 4.9 mmol/kgFFM*360 min (p=0.09 vs maltodextrin), which was lower than sucrose [11.1 ± 3.9 mmol/kgFFM*360 min (p=0.01 vs lactose)]. These data are consistent with the hypothesis that hepatic de novo lipogenesis contributes to both lactose and sucrose-induced lipaemia and provide a rationale to investigate the longer-term effects of lactose and sucrose on metabolism. [ABSTRACT FROM AUTHOR]

Nutrition and exercise metabolism are vibrant physiological fields, yet at times it feels as if greater progress could be made by better integrating these disciplines. Exercise is advocated for improving metabolic health, in part by increasing peripheral insulin sensitivity and glycaemic control. However, when a modest‐to‐high carbohydrate load is consumed before and/or during each exercise bout within a training programme, increases in oral glucose insulin sensitivity can be blunted in both men of a healthy weight and those with overweight/obesity. Exercise training‐induced adaptation in the energy sensing AMP‐activated protein kinase (AMPK) and the insulin‐sensitive glucose transporter GLUT4 protein levels are sensitive to pre‐exercise feeding status in both healthy individuals and individuals classified as overweight or obese. Increased lipid oxidation may, in part, explain the enhanced adaptive responses to exercise training performed before (i.e. fasted‐state exercise) versus after nutrient ingestion. Evidence in individuals with type 2 diabetes currently shows no effect of altering nutrient–exercise timing for measured markers of metabolic health, or greater reductions in glycated haemoglobin (HbA1c) concentrations with exercise performed after versus before nutrient provision. Since the metabolic inflexibility associated with type 2 diabetes diminishes differences in lipid oxidation between the fasted and fed states, it is plausible that pre‐exercise feeding status does not alter adaptations to exercise when metabolic flexibility is already compromised. Current evidence suggests restricting carbohydrate intake before and during exercise can enhance some health benefits of exercise, but in order to establish clinical guidelines, further research is needed with hard outcomes and different populations. [ABSTRACT FROM AUTHOR]

Key points: Ageing is associated with increased systemic inflammation and metabolic dysfunction that contributes to the development of age‐associated diseases.The role of adipose tissue in immunometabolic alterations that take place with ageing is unknown in humans.We show, in healthy, active and lean older adults, that adipose tissue, but not skeletal muscle, displays considerable pro‐inflammatory transcriptomic, cellular and secretory changes, as well as a reduction in insulin signalling proteins compared to younger adults.These findings indicate that adipose tissue undergoes substantial immunometabolic alterations with ageing, and that these changes are tissue‐specific and more profound than those observed in skeletal muscle or in the circulation.These results identify adipose tissue as an important tissue in the biological ageing process in humans, which may exhibit signs of immunometabolic dysfunction prior to systemic manifestation. Ageing and obesity are both characterized by inflammation and a deterioration in metabolic health. It is now clear that adipose tissue plays a major role in inflammation and metabolic control in obesity, although little is known about the role of adipose tissue in human ageing. To understand how ageing impacts adipose tissue, we characterized subcutaneous adipose tissue and skeletal muscle samples from twelve younger (27 ± 4 years [Young]) and twelve older (66 ± 5 years [Old]) active/non‐obese males. We performed a wide‐range of whole‐body and tissue measures, including RNA‐sequencing and multicolour flow cytometry. We also measured a range of inflammatory and metabolic proteins in the circulation and their release by adipose tissue, ex vivo. Both adipose tissue and muscle had ∼2‐fold more immune cells per gram of tissue with ageing. In adipose tissue, this immune cell infiltration was driven by increased memory/effector T‐cells, whereas, in muscle, the accumulation was driven by memory/effector T‐cells and macrophages. Transcriptomic analysis revealed that, with ageing, adipose tissue, but not muscle, was enriched for inflammatory transcripts/pathways related to acquired and innate immunity. Ageing also increased the adipose tissue pro‐inflammatory secretory profile. Insulin signalling protein content was reduced in adipose tissue, but not muscle. Our findings indicate that adipose tissue undergoes substantial immunometabolic changes with ageing in humans, and that these changes are tissue‐specific and more profound than those observed in the circulation and skeletal muscle. [ABSTRACT FROM AUTHOR]

Context: Adipose tissue and physical inactivity both influence metabolic health and systemic inflammation, but how adipose tissue responds to chronic physical inactivity is unknown. Objective: This work aimed to characterize the impact of chronic physical inactivity on adipose tissue in healthy, young males. Methods: We collected subcutaneous adipose tissue from 20 healthy, young men before and after 60 days of complete bed rest with energy intake reduced to maintain energy balance and fat mass. We used RNA sequencing, flow cytometry, ex vivo tissue culture, and targeted protein analyses to examine adipose tissue phenotype. Results: Our results indicate that the adipose tissue transcriptome, stromal cellular compartment, and insulin signaling protein abundance are largely unaffected by bed rest when fat mass is kept stable. However, there was an increase in the circulating concentration of several adipokines, including plasma leptin, which was associated with inactivity-induced increases in plasma insulin and absent from adipose tissue cultured ex vivo under standardized culture conditions. Conclusion: Physical inactivity-induced disturbances to adipokine concentrations such as leptin, without changes to fat mass, could have profound metabolic implications outside a clinical facility when energy intake is not tightly controlled. [ABSTRACT FROM AUTHOR]

Abnormalities in intracellular pH regulation have been proposed to be important in type 2 diabetes and the associated cardiomyopathy and hypertension. We have therefore investigated the dependence of insulin-stimulated glucose transport on cytosolic pH in cardiomyocytes. Insulin treatment of cardiomyocytes resulted in a marked alkalinization of the cytoplasm as measured using carboxy-semi-napthorhodofluor-1. The alkalinizing effect of insulin was blocked by treatment with either cariporide (which inhibits the [Na.sup.+]/[H.sup.+] exchanger) or by bafilomycin A1 (which inhibits [H.sup.+]-ATPase activity). After treatments with cariporide or bafilomycin A1, insulin stimulation of insulin receptor and insulin receptor substrate-1 phosphorylation and Akt activity were normal. In contrast, glucose transport activity and the levels of functional GLUT4 at the plasma membrane (detected using an exofacial photolabel) were reduced by ~50%. Immunocytochemical analysis revealed that insulin treatment caused a translocation of the GLUT4 from perinuclear structures and increased its co-localization with cell surface syntaxin 4. However, neither cariporide nor bafilomycin A1 treatment reduced the translocation of immunodetectable GLUT4 to the sarcolemma region of the cell. It is therefore hypothesized that insulin-stimulated cytosol alkalinization facilitates the final stages of translocation and incorporation of fully functional GLUT4 at the surface-limiting membrane. GLUT4 translocation; cytosolic pH; cariporide; bafilomycin A1

The mechanism of arachidonic acid release from vascular smooth muscle during oxidative stress is investigated using hydrogen peroxide. Results reveal that treatment with hydrogen peroxide inhibited the incorporation of arachidonic acid to the lipid component of the cell membrane. This impairment in reesterification is responsible for the accumulation and subsequent release of arachidonic acid during oxidative stress.

In the Arbuckle area of the Sacramento Valley, a 22-acre orchard was planted in 1990 with four almond varieties (‘Nonpareil’, ‘Butte’, ‘Carmel’ and ‘Monterey’). The orchard was irrigated with three types of microirrigation — surface drip, subsurface drip and microsprinklers. The orchard soils are 3 to 4 feet of gravelly, loamy sand overlaying a restricting clay layer. The coarse-textured soil with its low water-holding capacity allows little lateral movement of water from the microirrigation emission device. Under these soil conditions, microsprinkler-irrigated trees produced larger almond yields and showed greater tree growth. In addition, irrigation system evaluations show that all three microirrigation systems provide excellent irrigation uniformity levels after 8 years of operation with only routine maintenance.