Acute effects of active breaks during prolonged sitting on subcutaneous adipose tissue gene expression: an ancillary analysis of a randomised controlled trial.

Active breaks in prolonged sitting has beneficial impacts on cardiometabolic risk biomarkers. The molecular mechanisms include regulation of skeletal muscle gene and protein expression controlling metabolic, inflammatory and cell development pathways. An active communication network exists between adipose and muscle tissue, but the effect of active breaks in prolonged sitting on adipose tissue have not been investigated. This study characterized the acute transcriptional events induced in adipose tissue by regular active breaks during prolonged sitting. We studied 8 overweight/obese adults participating in an acute randomized three-intervention crossover trial. Interventions were performed in the postprandial state and included: (i) prolonged uninterrupted sitting; or prolonged sitting interrupted with 2-minute bouts of (ii) light- or (iii) moderate-intensity treadmill walking every 20 minutes. Subcutaneous adipose tissue biopsies were obtained after each condition. Microarrays identified 36 differentially expressed genes between the three conditions (fold change ≥0.5 in either direction; p < 0.05). Pathway analysis indicated that breaking up of prolonged sitting led to differential regulation of adipose tissue metabolic networks and inflammatory pathways, increased insulin signaling, modulation of adipocyte cell cycle, and facilitated cross-talk between adipose tissue and other organs. This study provides preliminary insight into the adipose tissue regulatory systems that may contribute to the physiological effects of interrupting prolonged sitting

Effects of the nitric oxide donor, sodium nitroprusside, on resting leg glucose uptake in patients with type 2 diabetes

Nitric oxide (NO) has been implicated as an important signalling molecule in the contraction-mediated glucose uptake pathway and may represent a novel strategy for blood glucose control. The current study sought to determine whether acute infusion of the NO donor, sodium nitroprusside (SNP), increases leg glucose uptake at rest in patients with type 2 diabetes

The effect of nitric oxide donor sodium nitroprusside on glucose uptake in human primary skeletal muscle cells

Nitric oxide (NO) has been implicated as an important signaling molecule in the insulin-independent, contraction-mediated glucose uptake pathway and may represent a novel strategy for blood glucose control in patients with type 2 diabetes (T2DM). The current study sought to determine whether the NO donor, sodium nitroprusside (SNP) increases glucose uptake in primary human skeletal muscle cells (HSkMC) derived from both healthy individuals and patients with T2DM. Vastus lateralis muscle cell cultures were derived from seven males with T2DM (aged 54 &plusmn; 2 years, BMI 31.7 &plusmn; 1.2 kg/m2, fasting plasma glucose 9.52 &plusmn; 0.80 mmol/L) and eight healthy individuals (aged 46 &plusmn; 2 years, BMI 27.1 &plusmn; 1.5 kg/m2, fasting plasma glucose 4.69 &plusmn; 0.12 mmol/L). Cultures were treated with both therapeutic (0.2 and 2 &mu;M) and supratherapeutic (3, 10 and 30 mM) concentrations of SNP. An additional NO donor S-nitroso-N-acetyl-D,L-penicillamine (SNAP) was also examined at a concentration of 50 &mu;M. Glucose uptake was significantly increased following both 30 and 60 min incubations with the supratherapeutic SNP treatments (P = 0.03) but not the therapeutic SNP doses (P = 0.60) or SNAP (P = 0.54). There was no difference in the response between the healthy and T2DM cell lines with any treatment or dose. The current study demonstrates that glucose uptake is elevated by supratherapeutic, but not therapeutic doses of SNP in human primary skeletal muscle cells derived from both healthy volunteers and patients with T2D. These data confirm that nitric oxide donors have potential therapeutic utility to increase glucose uptake in humans, but that SNP only achieves this in supratherapeutic doses. Further study to delineate mechanisms and the therapeutic window is warranted.<br /

The relationship between heat shock protein 72 expression in skeletal muscle and insulin sensitivity is dependent on adiposity

Decreased gene expression of heat shock protein 72 (HSP72) in skeletal muscle is associated with insulin resistance in humans. We aimed to determine whether HSP72 protein expression in insulin-sensitive tissues is related to criterion standard measures of adiposity and insulin resistance in a young healthy human population free of hyperglycemia. Healthy participants (N = 17; age, 30 ± 3 years) underwent measurement of body composition (dual-energy x-ray absorptiometry), a maximum aerobic capacity test (V̇o2max), an oral glucose tolerance test, and a hyperinsulinemic-euglycemic clamp (M) to access insulin sensitivity. Skeletal muscle and subcutaneous adipose tissue biopsies were obtained by percutaneous needle biopsy. HSP72 protein expression in skeletal muscle was inversely related to percentage body fat (r = −0.54, P < .05) and remained significant after adjustment for age and sex (P < .05). Insulin sensitivity was also related to HSP72 protein expression in skeletal muscle (r = 0.52, P < .05); however, this relationship disappeared after adjustment for percentage body fat (P = .2). In adipose tissue, HSP72 protein expression was not related to adiposity or insulin sensitivity. Physical activity and aerobic fitness did not show any association with HSP72 protein expression in either tissue studied. A lower expression of HSP72 protein in human skeletal muscle was associated with increased adiposity and decreased insulin sensitivity in healthy individuals. These findings are consistent with rodent data suggesting that HSP72 stimulates fat oxidation with consequent reduction in fat storage and adiposity

Between-meal sucrose-sweetened beverage consumption impairs glycaemia and lipid metabolism during prolonged sitting: A randomized controlled trial

Background & aims: Chronic overconsumption of sugar-sweetened beverages (SSBs) is associated with unfavourable health effects, including promotion of obesity. However, the acute effects of consuming SSBs on glucose and lipid metabolism remain to be characterized in a real-world, post-prandial context of prolonged sitting. We quantified the acute effects of between-meal SSB consumption compared with water, on glucose and lipid metabolism in habitual soft drink consumers during prolonged sitting. Methods: Twenty-eight overweight or obese young adults [15 males; 23 ± 3 (mean ± SD) years, body mass index (BMI) 31.0 ± 3.6 kg/m) participated. During uninterrupted sitting and following standardized breakfast and lunch meals, each participant completed two 7-h conditions on separate days in a randomized, crossover design study. For each condition, participants consumed either a sucrose SSB or water mid-morning and mid-afternoon. Peak responses and total area under the curve (tAUC) over 7 h for blood glucose, insulin, C-peptide, triglyceride and non-esterified fatty acid (NEFA) concentrations were quantified and compared. Results: Compared to water, SSB consumption significantly increased the peak responses for blood glucose (20 ± 4% (mean ± SEM)), insulin (43 ± 15%) and C-peptide (21 ± 6%) concentrations. The tAUC for all these parameters was also increased by SSB consumption. The tAUC for triglycerides was 15 ± 5% lower after SSBs and this was driven by males (P < 0.05), as females showed no difference between conditions. The tAUC for NEFAs was 13 ± 5% lower after the SSB condition (P < 0.05). Conclusions: Between-meal SSB consumption significantly elevated plasma glucose responses, associated with a sustained elevation in plasma insulin throughout a day of prolonged sitting. The SSB-induced reduction in circulating triglycerides and NEFAs indicates significant modulation of lipid metabolism, particularly in males. These metabolic effects may contribute to the development of metabolic disease when SSB consumption is habitual and co-occurring with prolonged sitting. Clinical Trial Registry number: ACTRN12616000840482, https://anzctr.org.au/Trial/Registration/TrialReview.aspx?ACTRN=12616000840482

Adipogenic differentiation of cultured human primary subcutaneous white adipocye precursor cells.

<p>(a) After differentiation cells were fixed and stained with oil red-O; images shown are 10x magnification. (b) Lipid content was measured by quantification of oil red-O staining (absorbance at 495 nm) (n = 4). After differentiation cells were treated with vehicle (Veh, PBS) or 0.5 mM N⁶,2′-O-Dibutyryladenosine 3′,5′-cyclic monophosphate (db-cAMP) for 6 hours, and glycerol secretion into media was measured to determine rates of lipolysis. Glycerol secretion increased significantly with db-cAMP compared to vehicle treatment, but there was no difference between groups (*P<0.05 db-cAMP <i>vs</i> veh, n = 5).</p

Fold-change in UCP1 protein content post-differentiation compared with pre-differentiation (n = 4, L; Lean, O; Obese; *P<0.05 vs pre-differentiation, † P<0.05 vs Obese post-differentiation, pre-differentiation normalized to 1.0).

<p>Fold-change in UCP1 protein content post-differentiation compared with pre-differentiation (n = 4, L; Lean, O; Obese; *P<0.05 vs pre-differentiation, † P<0.05 vs Obese post-differentiation, pre-differentiation normalized to 1.0).</p

Correction to: Pioglitazone reduces cold-induced brown fat glucose uptake despite induction of browning in cultured human adipocytes: a randomised, controlled trial in humans (Diabetologia, 10.1007/s00125-017-4479-9)

The baseline insulin data given in Table 1 for the placebo group were incorrectly reported as 51 ± 10\ua0pmol/l instead of 48 ± 10\ua0pmol/l. This mistake also impacts on data reported in Table 4. The authors also note an error in the reported change in noradrenaline levels, from pre- to post-pioglitazone treatment (Table 4). The relevant rows from Tables 1 and 4 are reproduced here, with corrected data shown in bold. These corrections do not change the statistical significance of any comparison. (Table presented.)