Acute physical exercise increases the adaptor protein APPL1 in the hypothalamus of obese mice.

Adiponectin is considered an adipokine that has essential anti-inflammatory and insulin-sensitivity actions. The adaptor protein containing the pleckstrin homology domain, the phosphotyrosine-binding domain, and leucine zipper motif 1 (APPL1) is a protein involved in adiponectin signaling that plays a role in many physiological and pathophysiological processes. In the central nervous system, adiponectin can potentiate the effects of leptin in the arcuate proopiomelanocortin (POMC) neurons. However, the role of APPL1 in the hypothalamus is not well understood. Therefore, in this study, we explored the effects of acute physical exercise on APPL1 protein content in the hypothalamus and food intake control in leptin stimulated-obese mice. Here we show that acute exercise increased serum adiponectin levels and APPL1 content in the hypothalamus, which were followed by reduced food intake in obese mice. Further, at the molecular level, the exercised obese mice increased the protein kinase B (Akt) signaling in the hypothalamus and attenuated the mammalian homolog of Drosophila tribbles protein 3 (TRB3) levels. In conclusion, the results indicate physical exercise is capable of increasing APPL1 protein content in the hypothalamus of leptin stimulated-obese mice and modulating food intake.

Renal protection induced by physical exercise may be mediated by the irisin/AMPK axis in diabetic nephropathy.

In patients with diabetes, it has been suggested that physical exercise may reduce albuminuria and the progression of renal disease. However, the molecular mechanism by which physical exercise protects the kidney in diabetes remains poorly understood. The aim of the present study was to determine the contribution of muscle irisin secretion induced by aerobic physical exercise with the subsequent activation of AMPK for kidney protection under diabetic conditions. Aerobic physical exercise in rats protected the kidney in streptozotocin-induced diabetes. It reduced albuminuria, glomerular hypertrophy, and glomerular expression of collagen IV and fibronectin, as well as markers of kidney inflammation, when compared to sedentary diabetic rats. These effects were associated with elevation in muscle FNDC5/irisin and activity of AMPK in the diabetic kidney. However, the beneficial effects of exercise were lost when the diabetic rats were treated with CycloRGDyK, that in the bone it has been described as an irisin receptor blocker. In cultured human tubular (HK-2) cells, treatment with recombinant irisin counteracted the effect of high glucose in a dose-dependent manner. Irisin, per se, also activated AMPK in HK-2 cells. It is concluded that in diabetes, the renal protective effect of exercise may be mediated by the irisin/AMPK pathway.

Omega-3 from Flaxseed Oil Protects Obese Mice Against Diabetic Retinopathy Through GPR120 Receptor.

The chronic and low-grade inflammation induced by obesity seem to be the "first hit" to retinopathy associated to diabetes type 2. Herein, we hypothesized that omega-3 fatty acids from flaxseed oil enriched diet disrupt the pro-inflammatory status in the retina, protecting against retinopathy development. For eight weeks under a high-fat diet (HF), several physiological parameters were monitored to follow the metabolic homeostasis disruption. After this period, mice were treated with a HF substituted in part of lard by flaxseed oil (FS) for another eight weeks. Food behavior, weight gain, glucose and insulin sensitivity, electroretinography, RT-qPCR and western blots were carried out. The HF was able to induce a pro-inflammatory background in the retina, changing IL1ß and TNFα. VEGF, a master piece of retinopathy, had early onset increased also induced by HF. The FS-diet was able to decrease inflammation and retinopathy and improved retinal electro stimuli compared to HF group. GPR120 and GPR40 (G Protein-Coupled Receptors 120 and 40), an omega-3 fatty acid receptors, were detected in the retina for the first time. FS-diet modulated the gene expression and protein content of these receptors. Thus, unsaturated fatty acids protect the retina from diabetes type 2 mice model from disease progression.

Physical exercise reduces pyruvate carboxylase (PCB) and contributes to hyperglycemia reduction in obese mice.

The present study evaluated the effects of exercise training on pyruvate carboxylase protein (PCB) levels in hepatic tissue and glucose homeostasis control in obese mice. Swiss mice were distributed into three groups: control mice (CTL), fed a standard rodent chow; diet-induced obesity (DIO), fed an obesity-inducing diet; and a third group, which also received an obesity-inducing diet, but was subjected to an exercise training protocol (DIO + EXE). Protocol training was carried out for 1 h/d, 5 d/wk, for 8 weeks, performed at an intensity of 60% of exhaustion velocity. An insulin tolerance test (ITT) was performed in the last experimental week. Twenty-four hours after the last physical exercise session, the animals were euthanized and the liver was harvested for molecular analysis. Firstly, DIO mice showed increased epididymal fat and serum glucose and these results were accompanied by increased PCB and decreased p-Akt in hepatic tissue. On the other hand, physical exercise was able to increase the performance of the mice and attenuate PCB levels and hyperglycemia in DIO + EXE mice. The above findings show that physical exercise seems to be able to regulate hyperglycemia in obese mice, suggesting the participation of PCB, which was enhanced in the obese condition and attenuated after a treadmill running protocol. This is the first study to be aimed at the role of exercise training in hepatic PCB levels, which may be a novel mechanism that can collaborate to reduce the development of hyperglycemia and type 2 diabetes in DIO mice.