Increased Energy Expenditure, Lipolysis and Hyperinsulinemia Confer Resistance to Central Obesity and Type 2 Diabetes in Mice Lacking Alpha2α-Adrenoceptors

Q2 · MEDICINE

Article

Author: Savontaus, Eriika ; Manz, Georg ; Valve, Laura ; Joos, Thomas O ; Tuomainen, Katja ; Baur, Nadja ; Scheinin, Mika ; Ruohonen, Suvi T ; Ailanen, Liisa ; Röyttä, Matias

The alpha2A-adrenoceptors (α2A-ARs) are Gi-coupled receptors, which prejunctionally inhibit the release of norepinephrine (NE) and epinephrine (Epi), and postjunctionally inhibit insulin secretion and lipolysis. We have earlier shown that α2A–/– mice display sympathetic hyperactivity, hyperinsulinemia and improved glucose tolerance. Here we employed α2A–/– mice and placed the mice on a high-fat diet (HFD) to test the hypothesis that lack of α2A-ARs protects from diet-induced obesity and type 2 diabetes (T2D). In addition, a high-caloric diet was combined with running wheel exercise to test the interaction of diet and exercise. HFD was obesogenic in both genotypes, but α2A–/– mice accumulated less visceral fat than the wild-type controls, were protected from T2D, and their insulin secretion was unaltered by the diet. Lack of α2A-ARs is associated with an increased sympatho-adrenal tone, which resulted in increased energy expenditure and fat oxidation rate potentiated by HFD. Fittingly, α2A–/– mice displayed enhanced lipolytic responses to Epi, and increased faecal lipids suggesting altered fat mobilization and absorption. Subcutaneous white fat appeared to be thermogenically more active (measured as Ucp1 mRNA expression) in α2A–/– mice, and brown fat showed an increased response to NE. Exercise was effective in reducing total body adiposity and increasing lean mass in both genotypes, but there was a significant diet-genotype interaction, as even modestly increased physical activity combined with lack of α2A-AR signalling promoted weight loss more efficiently than exercise with normal α2A-AR function. These results suggest that blockade of α2A-ARs may be exploited to reduce visceral fat and to improve insulin secretion.

01 Nov 2014·Journal of AOAC INTERNATIONALQ4 · AGRICULTURAL & FORESTRY SCIENCE

Validation Study of a HistaSure™ ELISAFast Track for the Determination of Histamine in Fish Samples

Q4 · AGRICULTURAL & FORESTRY SCIENCE

Article

Author: Manz, Georg ; Booltink, Esther ; Hungerford, James ; Mireles De Witt, Christina A. ; Koese, Sevim

AbstractLDN Labor Diagnostika Nord GmbH & Co. KG has developed an ELISA for the rapid semiquantitative or quantitative determination of histamine in different kinds of fish samples. Fresh/frozen tuna, canned tuna, fresh/frozen mahi mahi, canned sardines, and fish meal were used to validate the method under the requirements of the AOAC Research Institute Performance Tested MethodsSM Program. The results all fell within the defined acceptance criteria. Linearity was given throughout the 0–300 ppm measuring range. Cross reactivity to similarly structured food spoilage indicators (tyramine and cadaverine) was minimal, less than 1%. Overall recoveries for all tested matrixes were within the determined acceptable range (80–120%), and the repeatability of precision was less than 10% overall and less than 5% at the defect action level of 50 ppm set by the U.S. Food and Drug Administration. The LOQ for the ELISA was determined to be 1.27 ppm. No lot-to-lot differences were observed. A 2-year claimed shelf life, at 2–8°C, was confirmed through accelerated stability testing. After the introduction of minor procedural variations to the test, no differences in histamine levels were observed. Independent lab testing revealed that the ELISA works as well in the hands of minimally trained technicians as it does with expert developers. A strong correlation (r = 0.97) between the LDN ELISA and the AOAC 977.13 fluorometric method was observed. This study revealed that the LDN ELISA is equivalent to the AOAC Official Method977.13 for the precise and accurate measurement of histamine in fresh/frozen tuna, canned tuna, fresh/frozen mahi mahi, canned sardines, and fish meal.

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