The literature describes a close correlation between metabolic disorders and abnormal immune responses, like low-grade inflammation (LGI), which may be one mechanistic link between obesity and various comorbidities, including non-alcoholic fatty liver disease (NAFLD). In our study, we investigated the influence of dietary composition on obesity-derived LGI in the liver. We used a dietary induced obesity mouse model of C57BL/6J mice fed with high fat diet (HFD, 60% fat, 20% protein, 20% carbohydrates) and two different controls. One was rich in carbohydrates (10% fat, 20% protein, 70% carbohydrates), further referred to as the control diet (CD), and the other one is referred to as the standard diet (SD), with a more balanced macronutrient content (9% fat, 33% protein, 58% carbohydrates). Our results showed a significant increased NAFLD activity score in HFD compared to both controls, but livers of the CD group also differed in their macroscopic appearance from healthy livers. Hepatic fat content showed significantly elevated cholesterol concentrations in the CD group. Histologic analysis of the cellular immune response in the liver showed no difference between HFD and CD and expression analysis of immunologic mediators like interleukin (IL)-1β, IL-6, IL-10 and tumor necrosis factor alpha also point towards a pro-inflammatory response to CD, comparable to LGI in HFD. Therefore, when studying diet-induced obesity with a focus on inflammatory processes, we encourage researchers to carefully select controls and not use a control diet disproportionally rich in carbohydrates.
Caloric restriction (CR) slows the aging process, extends lifespan, and exerts neuroprotective effects. It is widely accepted that CR attenuates β-amyloid (Aβ) neuropathology in models of Alzheimer’s disease (AD) by so-far unknown mechanisms. One promising process induced by CR is autophagy, which is known to degrade aggregated proteins such as amyloids. In addition, autophagy positively regulates glucose uptake and may improve cerebral hypometabolism—a hallmark of AD—and, consequently, neural activity. To evaluate this hypothesis, APPswe/PS1delta9 (tg) mice and their littermates (wild-type, wt) underwent CR for either 16 or 68 weeks. Whereas short-term CR for 16 weeks revealed no noteworthy changes of AD phenotype in tg mice, long-term CR for 68 weeks showed beneficial effects. Thus, cerebral glucose metabolism and neuronal integrity were markedly increased upon 68 weeks CR in tg mice, indicated by an elevated hippocampal fluorodeoxyglucose [18F] ([18F]FDG) uptake and increased N-acetylaspartate-to-creatine ratio using positron emission tomography/computer tomography (PET/CT) imaging and magnet resonance spectroscopy (MRS). Improved neuronal activity and integrity resulted in a better cognitive performance within the Morris Water Maze. Moreover, CR for 68 weeks caused a significant increase of LC3BII and p62 protein expression, showing enhanced autophagy. Additionally, a significant decrease of Aβ plaques in tg mice in the hippocampus was observed, accompanied by reduced microgliosis as indicated by significantly decreased numbers of iba1-positive cells. In summary, long-term CR revealed an overall neuroprotective effect in tg mice. Further, this study shows, for the first time, that CR-induced autophagy in tg mice accompanies the observed attenuation of Aβ pathology.
ZusammenfasssungDer Geruchssinn ist wichtig. Das wurde insbesondere v. a. Patient:innen mit infektbedingtem Riechverlust während der SARS-CoV2 Pandemie bewusst. Wir reagieren z. B. auf Körpergerüche unserer Mitmenschen – die Nase bestimmt/wen wir „riechen können“. Der Geruchssinn warnt uns vor Gefahren, die Wahrnehmung von Düften und die Wahrnehmung von Aromen beim Essen bedeuten Lebensqualität. Eine Anosmie muss daher ernst genommen werden. Obwohl sich olfaktorische Rezeptorneurone durch Regenerationsfähigkeit auszeichnen, sind Anosmien mit etwa 5% relativ häufig. Riechstörungen werden nach der Ursache eingeteilt (z. B. Infekte, Schädelhirntraumen, chronische Rhinosinusitis, Alter) mit den sich daraus ergebenden unterschiedlichen Therapieoptionen und Prognosen. Eine gründliche Anamnese ist deshalb bedeutsam. Zur Diagnostik stehen verschiedenste Untersuchungsverfahren zur Verfügung, von orientierenden Kurztests über ausführliche mehrdimensionale Testverfahren bis hin zu elektrophysiologischen und bildgebenden Methoden. Damit sind quantitative Riechstörungen gut erfassbar und nachverfolgbar. Bei qualitativen Riechstörungen wie der Parosmie stehen derzeit allerdings keine objektivierenden Diagnoseverfahren zur Verfügung. Die therapeutischen Möglichkeiten bei Riechstörungen sind begrenzt. Trotzdem stehen mit dem Riechtraining sowie verschiedenen additiven medikamentösen Möglichkeiten wirksame Optionen zur Verfügung. Von großer Bedeutung ist nach wie vor die Beratung und das kompetente Gespräch mit den Patient:innen.
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