Gut microbiota play important roles in host metabolism, especially in diabetes. However, why different diets lead to similar diabetic states despite being associated with different microbiota is not clear. Mice were fed two high-energy diets (HED) with the same energy density but different fat-to-sugar ratios to determine the associations between the microbiota and early-stage metabolic syndrome. The two diets resulted in different microbiota but similar diabetic states. Interestingly, the microbial gene profiles were not significantly different, and many common metabolites were identified, including l-aspartic acid, cholestan-3-ol (5β, 3α), and campesterol, which have been associated with lipogenesis and inflammation. Our study suggests that different metabolic-syndrome-inducing diets may result in different microbiota but similar microbiomes and metabolomes. This suggests that the metagenome and metabolome are crucial for the prognosis and pathogenesis of obesity and metabolic syndrome.
IMPORTANCE Various types of diet can lead to type 2 diabetes. The gut microbiota in type 2 diabetic patients are also different. So, two questions arise: whether there are any commonalities between gut microbiota induced by different pro-obese diets and whether these commonalities lead to disease. Here we found that high-energy diets with two different fat-to-sugar ratios can both cause obesity and prediabetes but enrich different gut microbiota. Still, these different gut microbiota have similar genetic and metabolite compositions. The microbial metabolites in common between the diets modulate lipid accumulation and macrophage inflammation in vivo and in vitro. This work suggests that studies that only use 16S rRNA amplicon sequencing to determine how the microbes respond to diet and associate with diabetic state are missing vital information.
Salidroside, an active ingredient in Rhodiola rosea, has potent protective activity against cerebral ischemia. However, the mechanisms underlying its pharmacological actions are poorly understood. In this study, we employed a mouse middle cerebral artery occlusion (MCAO) and cellular oxygen and glucose deprivation (OGD) models to test the hypothesis that salidroside may restore mitochondrial quality control in neurons by modulating the relevant signaling. The results indicated that salidroside mitigated almost 40% the ischemia-induced brain infarct volumes in mice and the OGD-decreased viability of neurons to ameliorate the mitochondrial functions. Furthermore, salidroside treatment alleviated the OGD- or ischemia-induced imbalance of mitochondrial fission and fusion, mitophagy and promoted mitochondrial biogenesis in neurons by attenuating the AMPK activity. Moreover, salidroside alleviated 50% the OGD-promoted mitochondrial calcium fluorescence intensity and 5% mitochondria-associated membrane (MAM) area by down-regulating GRP75 expression independent of the AMPK signaling. Finally, similar findings were achieved in primary mouse neurons. Collectively, these data indicate that salidroside effectively restores the mitochondria dynamics, facilitates mitochondrial biogenesis by attenuating the AMPK signaling, and maintains calcium homeostasis in neurons independent of the AMPK activity.
Diabetic encephalopathy (DE) is a common complication of type 2 diabetes (T2D), especially in those patients with long T2D history. Persistent high glucose (HG) stimulation leads to neuron damage and manifests like Alzheimer's disease's pathological features such as neurofilament tangle. However, the precise mechanism of high‐glucose‐induced tau hyperphosphorylation is not fully revealed. We here gave evidence that Disrupted in schizophrenia 1 protein (DISC1) could interact with glycogen synthase kinase 3β (GSK3β) and inhibit its activity to prevent tau hyperphosphorylation. By using DB/DB mice as animal model and HG‐treated N2a cell as cell model, we found that DISC1 was downregulated both in vivo and in vitro, complicated with Tau hyperphosphorylation and GSK3β activation. Further, we identified DISC1 interacted with GSK3β by its 198th–237th amino acid residues. Overexpression of full length DISC1 but not mutated DISC1 lacking this domain could prevent HG induced tau hyperphosphorylation. Taken together, our work revealed DISC1 could be an important negative modulators of tau phosphorylation, and suggested that preservation of DISC1 could prevent HG induced neuron damage.
We study two families of orthogonal polynomials. The first is a finite family related to the Askey-Wilson polynomials but the orthogonality is on R. A limiting case of this family is an infinite system of orthogonal polynomials whose moment problem is indeterminate. We provide several orthogonality measures for the infinite family and derive their Plancherel-Rotach asymptotics.
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