Objective: PGC-1a is a transcriptional co-activator and master regulator of mitochondrial biogenesis. While extensively studied in skeletal and cardiac muscle, recent findings suggest that white adipose tissue PGC-1a plays an important role in regulating glucose homeostasis. The purpose of the present investigation was to evaluate the role of AMPK in regulating PGC-1a and mitochondrial enzymes in mouse epididymal and inguinal subcutaneous adipose tissue. Methods: Mitochondrial protein content and norepinephrine and CL 316,243-induced PGC-1a mRNA expression were studied in mouse epididymal and inguinal adipose tissue from wild-type and AMPK b1 2=2 mice. Results: The protein content and phosphorylation of AMPKa was reduced in epididymal adipose tissue from AMPK b1 2=2 compared to WT mice, concomitant with decreases in PGC-1a and mitochondrial marker proteins. Norepinephrine and CL 316,243-mediated induction of PGC-1a were decreased in cultured epididymal adipose tissue from AMPK b1 2=2 relative to WT mice. In inguinal adipose tissue from AMPK b1 2=2 mice, mitochondrial marker protein content and norepinephrine and CL 316,243-mediated increases in PGC-1a were normal despite reductions in the content and phosphorylation of AMPKa. Conclusions: Norepinephrine-and CL 316,243-mediated induction of PGC-1a and mitochondrial protein expression is regulated by AMPK in epididymal, but not inguinal adipose tissue.

Aims/hypothesis Consuming a high-fat diet (HFD) induces insulin resistance in white adipose tissue (WAT) within 1 week. However, little is known about the initiating events. One potential mechanism that has remained largely unexplored is excessive mitochondrial emission of reactive oxygen species (ROS). Methods To determine the role of mitochondrial ROS emissions at the onset of insulin resistance, wild-type (WT) mice were placed on an HFD for 1 week. WAT insulin sensitivity and inflammation were assessed by western blot. In addition, we optimised/validated a method to determine ROS emissions in permeabilised WAT. Results An HFD for 1 week resulted in impaired insulin signalling, increased c-Jun NH 2 -terminal kinase (JNK) phosphorylation and an increase in oxidative stress. These changes were associated with an increase in fatty-acid-mediated mitochondrial ROS emissions without any change in mitochondrial respiration/content. To determine that mitochondrial ROS causes insulin resistance, we used transgenic mice that express human catalase in mitochondria (MCAT) as a model of upregulated mitochondrial antioxidant enzyme capacity. MCAT mice displayed attenuated mitochondrial ROS emission, preserved insulin signalling and no inflammatory response following an HFD. Conclusions/interpretation Findings from this study suggest that elevated mitochondrial ROS emission contributes to HFD-induced WAT insulin resistance.

Exercise training reduces systemic and adipose tissue inflammation. However, these beneficial effects seem to be largely tied to reductions in adipose tissue mass. The purpose of the present study was to determine if exercise training confers a protective effect against an acute inflammatory challenge. We hypothesized that the induction of inflammatory markers, such as interleukin 6 (IL-6), suppressor of cytokine signaling 3 (SOCS3), and TNF-α by the beta-3 adrenergic agonist CL 316,243 would be reduced in adipose tissue from trained mice and this would be associated with reductions in transient receptor potential cation channel 4 (TRPV4), a protein recently shown to regulate the expression of proinflammatory cytokines. Exercise training (4 wk of treadmill running, 1 h/day, 5 days/wk) increased markers of skeletal muscle mitochondrial content and the induction of PPAR-gamma coactivator 1 alpha in epididymal adipose tissue. The mRNA expression of IL-6, SOCS3, and TNFα were not different in subcutaneous and epididymal adipose tissue from sedentary and trained mice; however, the CL 316,243-mediated induction of these genes was attenuated ∼50% in epididymal adipose tissue from trained mice as were increases in plasma IL-6. The effects of training were not explained by reductions in lipolytic responsiveness, but were associated with decreases in TRPV4 protein content. These results highlight a previously unappreciated anti-inflammatory effect of exercise training on adipose tissue immunometabolism and underscores the value of assessing adipose tissue inflammation in the presence of an inflammatory insult.

The purpose of this investigation was to determine whether exercise-induced increases in adipose tissue interleukin 6 (IL-6) signaling occurred as part of a larger proinflammatory response to exercise and whether the induction of IL-6 signaling with acute exercise was altered in trained mice in parallel with changes in the IL-6 receptor complex. Sedentary and trained C57BL/6J mice were challenged with an acute bout of exercise. Adipose tissue and plasma were collected immediately and 4 h afterward and analyzed for changes in indices of IL-6 signaling, circulating IL-6, markers of adipose tissue inflammation, and expression/content of IL-6 receptor and glycoprotein 130 (gp130). In untrained mice, IL-6 mRNA increased immediately after exercise, and increases in indices of IL-6 signaling were increased 4 h after exercise in epididymal, but not inguinal adipose tissue. This occurred independent of increases in plasma IL-6 and alterations in markers of inflammation. When compared with untrained mice, in trained mice, acute exercise induced the expression of gp130 and IL-6 receptor alpha (IL-6Rα), and training increased the protein content of these. Acute exercise induced the expression, and training increased the protein content, of glycoprotein 130 and IL-6Rα and was associated with a more rapid increase in markers of IL-6 signaling in epididymal adipose tissue from trained compared with untrained mice. The ability of exogenous IL-6 to increase phosphorylation of STAT3 was similar between groups. Our findings demonstrate that acute exercise increases IL-6 signaling in a depot-dependent manner, likely through an autocrine/paracrine mechanism. This response is initiated more rapidly after exercise in trained mice, potentially as a result of increases in IL-6Rα and gp130.

Mannoheptulose (MH), a sugar found in avocados that inhibits glycolysis in vitro, has been preliminarily investigated as a novel food ingredient for dogs. This study aimed to determine the effects of dietary MH, delivered as an extract of un-ripened avocado, on energy expenditure (EE) in healthy adult Labrador Retriever dogs (total of 12 dogs, 26.99 ± 0.634 kg, 4.9 ± 0.2 y). The study was a double-blind, cross-over with each dog receiving both dietary treatments, control (CON) and MH (400 mg/kg of diet; 6 mg/kg BW), in random order. Resting and post-prandial (10 h) EE and respiratory quotient (RQ) were determined by indirect calorimetry (d 42). The following day, body composition was assessed using dual X-ray absorptiometry. Continuous activity monitoring was conducted using an Atical® accelerometer (d 43–47). A vastus lateralis muscle biopsy was obtained prior to the morning meal (d 49) and 4 h after consumption of their meal (d 56) to determine the protein content and phosphorylation of 5' adenosine monophosphate-activated protein kinase (AMPK). Diet did not affect body weight, resting EE or skeletal muscle AMPK phosphorylation. Dogs fed MH had significantly lower post-prandial RQ (p = 0.02) and ratio of fat to lean body mass (p = 0.02). Physical activity during light time periods (but not dark) was lower in dogs fed MH (p < 0.05) during weekends, but not on weekdays. These results suggest that MH affects energy balance of adult dogs, but that these effects are not dose dependent and not due to physical activity.