English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

Background  Neuronatin (NNAT) is an endoplasmic reticulum proteolipid implicated in intracellular signalling.  Nnat  is highly-expressed in the hypothalamus, where it is acutely regulated by nutrients and leptin.  Nnat  pre-mRNA is differentially spliced to create  Nnat -α and -β isoforms. Genetic variation of  NNAT  is associated with severe obesity. Currently, little is known about the long-term regulation of  Nnat .    Methods  Expression of  Nnat  isoforms were examined in the hypothalamus of mice in response to acute fast/feed, chronic caloric restriction, diet-induced obesity and modified gastric bypass surgery.  Nnat  expression was assessed in the central nervous system and gastrointestinal tissues. RTqPCR was used to determine isoform-specific expression of  Nnat  mRNA.    Results  Hypothalamic expression of both  Nnat  isoforms was comparably decreased by overnight and 24-h fasting.  Nnat  expression was unaltered in diet-induced obesity, or subsequent switch to a calorie restricted diet.  Nnat  isoforms showed differential expression in the hypothalamus but not brainstem after bypass surgery. Hypothalamic  Nnat -β expression was significantly reduced after bypass compared with sham surgery (P = 0.003), and was positively correlated with post-operative weight-loss (R 2  = 0.38, P = 0.01). In contrast,  Nnat -α expression was not suppressed after bypass surgery (P = 0.19), and expression did not correlate with reduction in weight after surgery (R 2  = 0.06, P = 0.34). Hypothalamic expression of  Nnat -β correlated weakly with circulating leptin, but neither isoform correlated with fasting gut hormone levels post- surgery.  Nnat  expression was detected in brainstem, brown-adipose tissue, stomach and small intestine.    Conclusions    Nnat  expression in hypothalamus is regulated by short-term nutrient availability, but unaltered by diet-induced obesity or calorie restriction. While Nnat isoforms in the hypothalamus are co-ordinately regulated by acute nutrient supply, after modified gastric bypass surgery  Nnat  isoforms show differential expression. These results raise the possibility that in the radically altered nutrient and hormonal milieu created by bypass surgery, resultant differential splicing of  Nnat  pre-mRNA may contribute to weight-loss.

Differential Pre-mRNA Splicing Regulates Nnat Isoforms in the Hypothalamus after Gastric Bypass Surgery in Mice