Abstract:ObjectiveProkineticin 2 (PROK2) is a hypothalamic neuropeptide that plays a critical role in the rhythmicity of physiological functions and inhibits food intake. PROK2 is also expressed in the main olfactory bulb (MOB) as an essential factor for neuro-and morphogenesis. Since the MOB was shown to be strongly involved in eating behavior, we hypothesized that PROK2 could be a new target in the regulation of food intake and energy homeostasis, through its effects in the MOB. We also asked whether PROK2 could be a… Show more
“…None of these genes had a highly conserved non-synonymous variant that is expected to be damaging. Foxp1 has previously been shown to regulate hepatic glucose homeostasis 45 , and insulin stimulated glucose uptake 46 , making it a strong candidate, although both Gpr27 47 , 48 and Prok2 49 also play a role in glucose related phenotypes. Figure 7 Genome scans for select intermediary serum biochemistry measures.…”
Chronic kidney disease (CKD), which can ultimately progress to kidney failure, is influenced by genetics and the environment. Genes identified in human genome wide association studies (GWAS) explain only a small proportion of the heritable variation and lack functional validation, indicating the need for additional model systems. Outbred heterogeneous stock (HS) rats have been used for genetic fine-mapping of complex traits, but have not previously been used for CKD traits. We performed GWAS for urinary protein excretion (UPE) and CKD related serum biochemistries in 245 male HS rats. Quantitative trait loci (QTL) were identified using a linear mixed effect model that tested for association with imputed genotypes. Candidate genes were identified using bioinformatics tools and targeted RNAseq followed by testing in a novel in vitro model of human tubule, hypoxia-induced damage. We identified two QTL for UPE and five for serum biochemistries. Protein modeling identified a missense variant within Septin 8 (Sept8) as a candidate for UPE. Sept8/SEPTIN8 expression increased in HS rats with elevated UPE and tubulointerstitial injury and in the in vitro hypoxia model. SEPTIN8 is detected within proximal tubule cells in human kidney samples and localizes with acetyl-alpha tubulin in the culture system. After hypoxia, SEPTIN8 staining becomes diffuse and appears to relocalize with actin. These data suggest a role of SEPTIN8 in cellular organization and structure in response to environmental stress. This study demonstrates that integration of a rat genetic model with an environmentally induced tubule damage system identifies Sept8/SEPTIN8 and informs novel aspects of the complex gene by environmental interactions contributing to CKD risk.
“…None of these genes had a highly conserved non-synonymous variant that is expected to be damaging. Foxp1 has previously been shown to regulate hepatic glucose homeostasis 45 , and insulin stimulated glucose uptake 46 , making it a strong candidate, although both Gpr27 47 , 48 and Prok2 49 also play a role in glucose related phenotypes. Figure 7 Genome scans for select intermediary serum biochemistry measures.…”
Chronic kidney disease (CKD), which can ultimately progress to kidney failure, is influenced by genetics and the environment. Genes identified in human genome wide association studies (GWAS) explain only a small proportion of the heritable variation and lack functional validation, indicating the need for additional model systems. Outbred heterogeneous stock (HS) rats have been used for genetic fine-mapping of complex traits, but have not previously been used for CKD traits. We performed GWAS for urinary protein excretion (UPE) and CKD related serum biochemistries in 245 male HS rats. Quantitative trait loci (QTL) were identified using a linear mixed effect model that tested for association with imputed genotypes. Candidate genes were identified using bioinformatics tools and targeted RNAseq followed by testing in a novel in vitro model of human tubule, hypoxia-induced damage. We identified two QTL for UPE and five for serum biochemistries. Protein modeling identified a missense variant within Septin 8 (Sept8) as a candidate for UPE. Sept8/SEPTIN8 expression increased in HS rats with elevated UPE and tubulointerstitial injury and in the in vitro hypoxia model. SEPTIN8 is detected within proximal tubule cells in human kidney samples and localizes with acetyl-alpha tubulin in the culture system. After hypoxia, SEPTIN8 staining becomes diffuse and appears to relocalize with actin. These data suggest a role of SEPTIN8 in cellular organization and structure in response to environmental stress. This study demonstrates that integration of a rat genetic model with an environmentally induced tubule damage system identifies Sept8/SEPTIN8 and informs novel aspects of the complex gene by environmental interactions contributing to CKD risk.
“…Patients with type 2 diabetes often have varying degrees of insulin resistance, and insulin resistance is associated with higher levels of inflammation and changes in lipid metabolism. 15 – 17 Bifidobacteria and Akkermansia detected in patients with type 2 diabetes produce short-chain fatty acids, which are inversely associated with low-grade inflammation and insulin resistance. 18 The current study found that the richness of Megasphaera was higher in the DPN group than in the NC group, and HOMA-IR was positively correlated with the presence of Megasphaera (coccidia) in the DPN group, further confirming that the occurrence of insulin resistance plays an important role in DPN associated with type 2 diabetes.…”
Objective To study the characteristics of the intestinal flora in patients with diabetic peripheral neuropathy (DPN) and analyze the association between the intestinal flora and clinical indicators. Methods We classified 80 subjects into three groups: patients with DPN (n = 45), patients type 2 diabetes without DPN (n = 21), and healthy controls (n = 14). The intestinal flora composition was compared among the three groups, and the correlation between the intestinal flora and clinical indicators was analyzed. Results At the phylum level, the richness of Firmicutes and Actinobacteria was elevated in the DN group, and that of Bacteroidetes was decreased. At the genus level, the richness of Bacteroides and Faecalibacterium was significantly decreased in the DPN group, whereas that of Escherichia- Shigella, Lachnoclostridium, Blautia, Megasphaera, and Ruminococcus torques group was increased. The homeostasis model assessment insulin resistance index was positively correlated with Megasphaera richness. Glycine ursodeoxycholic acid was positively correlated with Ruminococcus gnavus group and Phascolarctobacterium richness. Tauroursodeoxycholic acid was positively correlated with Ruminococcus gnavus group and Parabacteroides richness. Conclusion There was obvious intestinal microbiota disorder in patients with DPN, which may be related to insulin resistance. These changes may have important roles in the development of DPN.
“…People suffering from OI might either maintain their weight, or eat less, or on the contrary eat more since food would become tasteless; reasons for this remain unclear (Croy et al, 2014). Interestingly, there is growing evidence that the olfactory system could greatly contribute in the regulation of food intake and energy balance, through its effect on sympathetic and parasympathetic tone (Palouzier-Paulignan et al, 2012;Garrison and Knight, 2017;Mortreux et al, 2019). Indeed, receptors to a variety of orexigenic and anorexigenic molecules (i.e., insulin, leptin, ghrelin, neuropeptide Y, nutrient glucose) were found in the olfactory epithelium and in the olfactory bulb (Palouzier-Paulignan et al, 2012;Min and Min, 2018).…”
Section: Effects Of Olfactory Loss On Eating Behavior Danger Warningmentioning
Olfaction is a sense involved in a complex set of tasks, influencing eating behavior, increasing awareness of environmental hazards and affecting social communication. Surprisingly, smell disorders are very frequent, especially in the elderly population. Several recent studies conducted mostly in older subjects have demonstrated a strong association between olfactory impairment and overall mortality risk, with anosmia being even more predictive of 5 years mortality risk than cardiovascular disease. Presently, the underlying pathophysiology linking olfactory impairment to mortality remains unknown and only putative mechanisms are suggested. This review aims to examine the link between olfactory impairment and mortality and to discuss existing ideas on underlying existing mechanisms including, (1) the effect of olfactory loss on nutrition, life-threatening situations and social interactions, (2) associated neurodegenerative diseases, (3) accelerated brain aging, and (4) reflection of general health status being reflected in olfactory function.
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