Does prior acute exercise affect postexercise substrate oxidation in response to a high carbohydrate meal?

<p>Abstract</p> <p>Background</p> <p>Consumption of a mixed meal increases postprandial carbohydrate utilization and decreases fat oxidation. On the other hand, acute endurance exercise increases fat oxidation and decreases carbohydrate utilization during the post-exercise recovery period. It is possible that the resulting post-exercise increase in circulating nonesterified fatty acids could attenuate the ability of ingested carbohydrate to inhibit lipid oxidation. The purpose of this study was to determine whether prior exercise attenuates the usual meal-induced decline in lipid oxidation.</p> <p>Methods</p> <p>Six healthy, physically active young subjects (x age = 26.3 years, 4 males, 2 females) completed three treatments in random order after a ~10 h fast: (a) Exercise/Carbohydrate (Ex/CHO) – subjects completed a bout of exercise at 70% VO_2peak(targeted net energy cost of 400 kcals), followed by consumption of a carbohydrate-rich meal; (b) Exercise/Placebo (Ex/Placebo) – subjects completed an identical bout of exercise followed by consumption of a placebo; and (c) No Exercise/Carbohydrate (NoEx/CHO) – subjects sat quietly rather than exercising and then consumed the carbohydrate-rich meal. Blood samples were obtained before and during the postprandial period to determine plasma glucose, insulin, and non-esterified fatty acids (NEFA). Respiratory gas exchange measures were used to estimate rates of fat and carbohydrate oxidation.</p> <p>Results</p> <p>Plasma NEFA were approximately two-fold higher immediately following the two exercise conditions compared to the no-exercise condition, while meal consumption significantly increased insulin and glucose in both Ex/CHO and NoEx/CHO. NEFA concentrations fell rapidly during the 2-h postprandial period, but remained higher compared to the NoEx/CHO treatment. Carbohydrate oxidation increased rapidly and fat oxidation decreased in response to the meal, with no differences in the rates of carbohydrate and fat oxidation during recovery between the Ex/CHO and NoEx/CHO conditions.</p> <p>Conclusion</p> <p>The plasma NEFA concentration is increased during the post exercise period, which is associated with elevated fat oxidation when no meal is consumed. However, when a mixed meal is consumed immediately following exercise, the initially elevated plasma NEFA concentration decreases rapidly, and postexercise fat oxidation during this 2-h postexercise, postprandial period is no higher than that of the 2-h postprandial period without prior exercise.</p

Non-Image-Forming Light Driven Functions Are Preserved in a Mouse Model of Autosomal Dominant Optic Atrophy

Autosomal dominant optic atrophy (ADOA) is a slowly progressive optic neuropathy that has been associated with mutations of the OPA1 gene. In patients, the disease primarily affects the retinal ganglion cells (RGCs) and causes optic nerve atrophy and visual loss. A subset of RGCs are intrinsically photosensitive, express the photopigment melanopsin and drive non-image-forming (NIF) visual functions including light driven circadian and sleep behaviours and the pupil light reflex. Given the RGC pathology in ADOA, disruption of NIF functions might be predicted. Interestingly in ADOA patients the pupil light reflex was preserved, although NIF behavioural outputs were not examined. The B6; C3-Opa1Q285STOP mouse model of ADOA displays optic nerve abnormalities, RGC dendropathy and functional visual disruption. We performed a comprehensive assessment of light driven NIF functions in this mouse model using wheel running activity monitoring, videotracking and pupillometry. Opa1 mutant mice entrained their activity rhythm to the external light/dark cycle, suppressed their activity in response to acute light exposure at night, generated circadian phase shift responses to 480 nm and 525 nm pulses, demonstrated immobility-defined sleep induction following exposure to a brief light pulse at night and exhibited an intensity dependent pupil light reflex. There were no significant differences in any parameter tested relative to wildtype littermate controls. Furthermore, there was no significant difference in the number of melanopsin-expressing RGCs, cell morphology or melanopsin transcript levels between genotypes. Taken together, these findings suggest the preservation of NIF functions in Opa1 mutants. The results provide support to growing evidence that the melanopsin-expressing RGCs are protected in mitochondrial optic neuropathies

Effects of Male Hypogonadism on Regional Adipose Tissue Fatty Acid Storage and Lipogenic Proteins

Testosterone has long been known to affect body fat distribution, although the underlying mechanisms remain elusive. We investigated the effects of chronic hypogonadism in men on adipose tissue fatty acid (FA) storage and FA storage factors. Twelve men with chronic hypogonadism and 13 control men matched for age and body composition: 1) underwent measures of body composition with dual energy x-ray absorptiometry and an abdominal CT scan; 2) consumed an experimental meal containing [3H]triolein to determine the fate of meal FA (biopsy-measured adipose storage vs. oxidation); 3) received infusions of [U-13C]palmitate and [1-14C]palmitate to measure rates of direct free (F)FA storage (adipose biopsies). Adipose tissue lipoprotein lipase, acyl-CoA synthetase (ACS), and diacylglycerol acetyl-transferase (DGAT) activities, as well as, CD36 content were measured to understand the mechanism by which alterations in fat storage occur in response to testosterone deficiency. Results of the study showed that hypogonadal men stored a greater proportion of both dietary FA and FFA in lower body subcutaneous fat than did eugonadal men (both p<0.05). Femoral adipose tissue ACS activity was significantly greater in hypogonadal than eugonadal men, whereas CD36 and DGAT were not different between the two groups. The relationships between these proteins and FA storage varied somewhat between the two groups. We conclude that chronic effects of testosterone deficiency has effects on leg adipose tissue ACS activity which may relate to greater lower body FA storage. These results provide further insight into the role of androgens in body fat distribution and adipose tissue metabolism in humans

The individual environment, not the family is the most important influence on preferences for common non-alcoholic beverages in adolescence

Beverage preferences are an important driver of consumption, and strong liking for beverages high in energy (e.g. sugar-sweetened beverages [SSBs]) and dislike for beverages low in energy (e.g. non-nutritive sweetened beverages [NNSBs]) are potentially modifiable risk factors contributing to variation in intake. Twin studies have established that both genes and environment play important roles in shaping food preferences; but the aetiology of variation in non-alcoholic beverage preferences is unknown. 2865 adolescent twins (18–19-years old) from the Twins Early Development Study were used to quantify genetic and environmental influence on variation in liking for seven non-alcoholic beverages: SSBs; NNSBs; fruit cordials, orange juice, milk, coffee, and tea. Maximum Likelihood Structural Equation Modelling established that beverage preferences have a moderate to low genetic basis; from 18% (95% CI: 10%, 25%) for orange juice to 42% (36%, 43%) for fruit cordials. Aspects of the environment that are not shared by twin pairs explained all remaining variance in drink preferences. The sizeable unique environmental influence on beverage preferences highlights the potential for environmental modification. Policies and guidelines to change preferences for unhealthy beverages may therefore be best directed at the wider environment

Evaluation of nine candidate genes in patients with normal tension glaucoma: a case control study

<p>Abstract</p> <p>Background</p> <p>Normal tension glaucoma is a major subtype of glaucoma, associated with intraocular pressures that are within the statistically normal range of the population. Monogenic forms following classical inheritance patterns are rare in this glaucoma subtype. Instead, multigenic inheritance is proposed for the majority of cases. The present study tested common sequence variants in candidate genes for association with normal tension glaucoma in the German population.</p> <p>Methods</p> <p>Ninety-eight SNPs were selected to tag the common genetic variation in nine genes, namely OPTN (optineurin), RDX (radixin), SNX16 (sorting nexin 16), OPA1 (optic atrophy 1), MFN1 (mitofusin 1), MFN2 (mitofusin 2), PARL (presenilin associated, rhomboid-like), SOD2 (superoxide dismutase 2, mitochondrial) and CYP1B1 (cytochrome P450, family 1, subfamily B, polypeptide 1). These SNPs were genotyped in 285 cases and 282 fully evaluated matched controls. Statistical analyses comprised single polymorphism association as well as haplogroup based association testing.</p> <p>Results</p> <p>Results suggested that genetic variation in five of the candidate genes (RDX, SNX16, OPA1, SOD2 and CYP1B1) is unlikely to confer major risk to develop normal tension glaucoma in the German population. In contrast, we observed a trend towards association of single SNPs in OPTN, MFN1, MFN2 and PARL. The SNPs of OPTN, MFN2 and PARL were further analysed by multimarker haplotype-based association testing. We identified a risk haplotype being more frequent in patients and a vice versa situation for the complementary protective haplotype in each of the three genes.</p> <p>Conclusion</p> <p>Common variants of OPTN, PARL, MFN1 and MFN2 should be analysed in other cohorts to confirm their involvement in normal tension glaucoma.</p

Remodeling Lipid Metabolism and Improving Insulin Responsiveness in Human Primary Myotubes

OBJECTIVE: Disturbances in lipid metabolism are strongly associated with insulin resistance and type 2 diabetes (T2D). We hypothesized that activation of cAMP/PKA and calcium signaling pathways in cultured human myotubes would provide further insight into regulation of lipid storage, lipolysis, lipid oxidation and insulin responsiveness. METHODS: Human myoblasts were isolated from vastus lateralis, purified, cultured and differentiated into myotubes. All cells were incubated with palmitate during differentiation. Treatment cells were pulsed 1 hour each day with forskolin and ionomycin (PFI) during the final 3 days of differentiation to activate the cAMP/PKA and calcium signaling pathways. Control cells were not pulsed (control). Mitochondrial content, (14)C lipid oxidation and storage were measured, as well as lipolysis and insulin-stimulated glycogen storage. Myotubes were stained for lipids and gene expression measured. RESULTS: PFI increased oxidation of oleate and palmitate to CO(2) (p<0.001), isoproterenol-stimulated lipolysis (p = 0.01), triacylglycerol (TAG) storage (p<0.05) and mitochondrial DNA copy number (p = 0.01) and related enzyme activities. Candidate gene and microarray analysis revealed increased expression of genes involved in lipolysis, TAG synthesis and mitochondrial biogenesis. PFI increased the organization of lipid droplets along the myofibrillar apparatus. These changes in lipid metabolism were associated with an increase in insulin-mediated glycogen storage (p<0.001). CONCLUSIONS: Activation of cAMP/PKA and calcium signaling pathways in myotubes induces a remodeling of lipid droplets and functional changes in lipid metabolism. These results provide a novel pharmacological approach to promote lipid metabolism and improve insulin responsiveness in myotubes, which may be of therapeutic importance for obesity and type 2 diabetes

Mathematical modelling of clostridial acetone-butanol-ethanol fermentation

Clostridial acetone-butanol-ethanol (ABE) fermentation features a remarkable shift in the cellular metabolic activity from acid formation, acidogenesis, to the production of industrial-relevant solvents, solventogensis. In recent decades, mathematical models have been employed to elucidate the complex interlinked regulation and conditions that determine these two distinct metabolic states and govern the transition between them. In this review, we discuss these models with a focus on the mechanisms controlling intra- and extracellular changes between acidogenesis and solventogenesis. In particular, we critically evaluate underlying model assumptions and predictions in the light of current experimental knowledge. Towards this end, we briefly introduce key ideas and assumptions applied in the discussed modelling approaches, but waive a comprehensive mathematical presentation. We distinguish between structural and dynamical models, which will be discussed in their chronological order to illustrate how new biological information facilitates the ‘evolution’ of mathematical models. Mathematical models and their analysis have significantly contributed to our knowledge of ABE fermentation and the underlying regulatory network which spans all levels of biological organization. However, the ties between the different levels of cellular regulation are not well understood. Furthermore, contradictory experimental and theoretical results challenge our current notion of ABE metabolic network structure. Thus, clostridial ABE fermentation still poses theoretical as well as experimental challenges which are best approached in close collaboration between modellers and experimentalists