Lower Skeletal Muscle Mitochondrial Content After a High Fat Diet Rich in Polyunsaturated Fatty Acids Compared to a High Fat Diet Rich in Monounsaturated Fatty Acids

High fat diet (HFD) has been associated with weight gain, insulin resistance, and type 2 diabetes. The composition of fatty acids in various diets (monounsaturated, polyunsaturated, saturated) influence levels of blood insulin, glucose, and the onset of metabolic and cardiovascular diseases. PURPOSE: Determine the effects of high fat diets with alterations in the major dietary fatty acid content (a mixed fat western diet, a polyunsaturated fatty acid diet or a monounsaturated fatty acid diet) on skeletal muscle glycogen, lipid, glucose transporter 4 (GLUT4), and mitochondrial content. METHODS: Male Sprague Dawley rats were fed a 21% (by weight; 41% total energy) high fat western-style diet for 9 weeks to induce obesity. They were then divided into 3 dietary groups that continued on a HFD for the next 6 weeks of 1) mixed fat western diet (WD) (9.8% saturated, 7.7% mono; 3.5% poly; n=9); 2) monounsaturated fat (MUFA) (2.8% saturated, 15.8% mono; 2.2% poly; n=9); or 3) polyunsaturated fat (PUFA) (3.0% saturated; 2.9%mono; 15.7% poly; n=8). A control group followed a 15-week low fat Chow diet (CD) (4.8% fat; 0.74% saturated fat; 2% mono; 1.77% poly; n=9). At the end of the dietary intervention, glycogen content was measured in extensor digitorum longus (EDL) with periodic acid-schiff staining. GLUT4 protein content was measured using rabbit polyclonal antibody against GLUT4 (ab654), mitochondrial content was measured using mouse polyclonal antibody against COX4 protein (ab14744), and lipid content was measured using BODIPY 493/503, using immunohistochemistry techniques. Images were captured by ZEN imaging software by ZEIS and data was analyzed with ImageJ. RESULTS: There were no significant differences in glycogen content after 6 weeks of HFD with different dietary fatty acid composition, compared to control chow diet. (AU± SEM; CD: 4.41±0.04, WD: 4.74± 0.13, MUFA: 4.54± 0.08, PUFA: 4.54± 0.11, one-way ANOVA p= 0.11). There were also no significant differences in GLUT4 protein content (AU± SEM; CD: 74.68± 5.91, WD: 64.42 ± 2.88, MUFA: 76.12± 6.51, PUFA: 62.83± 4.12; one-way ANOVA p= 0.17) and lipid content after a HFD differing in dietary fatty acids compared to a control chow diet. (AU± SEM; CD: 168± 19.28, WD: 141.3 ± 15.5, MUFA: 193.7 ± 15.3, PUFA: 152.1± 16,69; one-way ANOVA p=0.18). Mitochondria content was less in HFD rich in PUFA when compared to HFD rich in MUFA (CD; WD; AU± SEM; MUFA 60.33±7.31 vs. PUFA 37.42±5.53; MUFA vs. PUFA p= 0.03). CONCLUSION: Our data suggest that six weeks of high fat diet does not affect skeletal muscle glycogen content, lipid content and GLUT4 content regardless of dietary fatty acid composition. Six weeks of high fat diet rich in polyunsaturated fatty acids results in lower mitochondrial content compared to high fat diet rich in monounsaturated fatty acid. Our data suggest that high fat diet rich in polyunsaturated fatty acids may negatively impact skeletal muscle oxidative capacity compared to a diet rich in monounsaturated fatty acids

High Fat Diet Rich in Saturated Fatty Acids, but Not Monounsaturated Fatty Acids, Impairs Glycogen Preservation after Adiponectin Treatment

High fat diet (HFD) is associated with the progression of obesity, type 2 diabetes and diminished insulin sensitivity, which is characterized by a lower glucose uptake and glycogen synthesis capacity in skeletal muscle. Adiponectin (Ad), on the other hand, is a cytokine secreted by adipose tissue that promotes glucose uptake and fatty acid oxidation in skeletal muscle. PURPOSE: To determine the effects of Ad on skeletal muscle glycogen, GLUT 4, mitochondrial and lipid content in animals fed with a HFD but with alterations in dietary fatty acids (mixed fat western diet and predominately monounsaturated fatty acid). METHODS: Male Sprague Dawley rats were fed a Western-style (21% fat) HFD for 9 weeks to induce obesity, then, for 6 weeks, continued the mixed fat Western diet (WD) (9.8% saturated fat; 7.7% mono; 3.5% poly; n=8) or a HFD high in monounsaturated fatty acids (MUFA) (21% fat; 17.76% mono; 1.8% poly; n=8). A control group followed a 15-week standard Chow diet (CD) (4.8% fat; 0.74% saturated fat; 2% mono; 1.77% poly; n=9). Right and left hind-leg extensor digitorum longus (EDL) muscles were incubated in an organ bath (containing Krebs-Henseleit buffer with 2000 mg/L glucose, without calcium chloride and sodium bicarbonate) with or without 0.1 mg/ml Ad for 30 minutes. Glycogen content in the EDL muscle was measured by using periodic acid-schiff staining, while GLUT 4 protein content was measured using rabbit polyclonal antibody against GLUT 4 (ab654), mitochondrial content was measured using a mouse polyclonal antibody against COX 4 protein (ab14744) and lipid content was measured using BODIPY 493/503, using immunohistochemistry techniques. Images were quantified with ImageJ software. RESULTS: The Ad incubation resulted in a decrease in muscle glycogen content in animas fed with WD (4.85 ± 0.13 to 4.29 ± 0.11 AU; p=0.05). This decrease in glycogen content in the WD group was significantly different compared to a better preservation of glycogen in both CD (p=0.04) and the MUFA diet groups (p=0.012) (CD: 0.11 ± 0.071 AU; WD: -0.25 ± 0.14 AU; MUFA: 0.18 ± 0.05 AU; one way ANOVA, p=0.01). Animals fed with CD tended to have a better preservation of lipid content compared to animals fed with WD (p=0.07) and a diet high in MUFA (p=0.09) (CD: 25.93 ± 11.2 AU; WD: -21.09 ± 14.81 AU; MUFA: 25.97 ± 16.17 AU; one way ANOVA, p=0.06). There were no significant changes in GLUT 4 and mitochondrial content regardless of diet and adiponectin incubation. CONCLUSIONS: Animals fed with a western style HFD rich in saturated fat show an impaired response to adiponectin induced increase/preservation of glycogen in skeletal muscle compared to a chow diet, as well as a HFD rich in MUFA. Diets high in saturated fatty acids may have an impaired response to adiponectin treatment

An analog of Heisenberg uncertainty relation in prequantum classical field theory

Prequantum classical statistical field theory (PCSFT) is a model which provides a possibility to represent averages of quantum observables, including correlations of observables on subsystems of a composite system, as averages with respect to fluctuations of classical random fields. PCSFT is a classical model of the wave type. For example, "electron" is described by electronic field. In contrast to QM, this field is a real physical field and not a field of probabilities. An important point is that the prequantum field of e.g. electron contains the irreducible contribution of the background field, vacuum fluctuations. In principle, the traditional QM-formalism can be considered as a special regularization procedure: subtraction of averages with respect to vacuum fluctuations. In this paper we derive a classical analog of the Heisenberg-Robertson inequality for dispersions of functionals of classical (prequantum) fields. PCSFT Robertson-like inequality provides a restriction on the product of classical dispersions. However, this restriction is not so rigid as in QM. The quantum dispersion corresponds to the difference between e.g. the electron field dispersion and the dispersion of vacuum fluctuations. Classical Robertson-like inequality contains these differences. Hence, it does not imply such a rigid estimate from below for dispersions as it was done in QM

Experimental tests of hidden variable theories from dBB to Stochastic Electrodynamics

In this paper we present some of our experimental results on testing hidden variable theories, which range from Bell inequalities measurements to a conclusive test of stochastic electrodynamics

About 1% of the breast and ovarian Spanish families testing negative for BRCA1 and BRCA2 are carriers of RAD51D pathogenic variants

RAD51D mutations have been recently identified in breast (BC) and ovarian cancer (OC) families. Although an etiological role in OC appears to be present, the association of RAD51D mutations and BC risk is more unclear. We aimed to determine the prevalence of germline RAD51D mutations in Spanish BC/OC families negative for BRCA1/BRCA2 mutations. We analyzed 842 index patients: 491 from BC/OC families, 171 BC families, 51 OC families and 129 patients without family history but with early-onset BC or OC or metachronous BC and OC. Mutation detection was performed with high-resolution melting, denaturing high-performance liquid chromatography or Sanger sequencing. Three mutations were found in four families with BC and OC cases (0.82%). Two were novel: c.1A>T (p.Met1?) and c.667+2_667+23del, leading to the exon 7 skipping and one previously described: c.674C>T (p.Arg232*). All were present in BC/OC families with only one OC. The c.667+2_667+23del cosegregated in the family with one early-onset BC and two bilateral BC cases. We also identified the c.629C>T (p.Ala210Val) variant, which was predicted in silico to be potentially pathogenic. About 1% of the BC and OC Spanish families negative for BRCA1/BRCA2 are carriers of RAD51D mutations. The presence of several BC mutation carriers, albeit in the context of familial OC, suggests an increased risk for BC, which should be taken into account in the follow-up and early detection measures. RAD51D testing should be considered in clinical setting for families with BC and OC, irrespective of the number of OC cases in the family