A gene that helps to control inflammation increases the risk of obesity and could be turned off in mice to stop weight gain, a study has found.
"We found small changes in the inflammatory gene RIPK1 in the obese people, and these variations caused an increased amount of the gene being present in their fat tissue, increasing their risk of being obese," the senior author said.
"RIPK1 is essential for a healthy immune response, but it also causes hyper-inflammation when it 'goes rogue'.
"By finding an increased amount of inflammation in obese people, we can confidently say that obesity increases inflammation."
The authors show that genetic polymorphisms near the human RIPK1 locus associate with increased RIPK1 gene expression and obesity. They show that one of these single nucleotide polymorphisms is within a binding site for E4BP4 and increases RIPK1 promoter activity and RIPK1 gene expression in adipose tissue.
The researchers then looked at the effect of turning the inflammatory gene on and off in mice. Therapeutic silencing of RIPK1 in vivo in a mouse model of diet-induced obesity dramatically reduces fat mass, total body weight and improves insulin sensitivity, while simultaneously reducing macrophage and promoting invariant natural killer T cell accumulation in adipose tissue.
The mice with a normal level of the inflammatory gene put on weight from eating the same high-fat diet.
More than half the 2000 participants were extremely obese with an average Body Max Index of 41 and half were a healthy weight.
The author said said that when stores exceeded healthy levels, the fat tissue became overwhelmed, cells died and the immune system was activated. "In obesity, the immune cells are working in overdrive, causing damaging inflammation when they don't switch off," the author said. "By understanding more about these inflammation pathways, we can find ways to intervene to treat obesity, especially in specific groups of people.
"These variations in the RIPK1 gene only occur in 8 to 12 per cent of the population - so maybe these are the people who struggle to lose weight despite doing all the right things."
https://www.uq.edu.au/news/article/2020/09/inflammatory-gene-provides-clue-obesity-risk
https://www.nature.com/articles/s42255-020-00279-2
Inflammatory gene implicated in obesity risk
- 1,888 views
- Added
Edited
Latest News
A new brain circuit in mice…
By newseditor
Posted 08 May
Mechanism of choline entry…
By newseditor
Posted 07 May
Link between UTI and breast…
By newseditor
Posted 07 May
Sleep resets brain connections
By newseditor
Posted 07 May
Interplay of various enzyme…
By newseditor
Posted 07 May
Other Top Stories
Gut bacterium trains infant immune system
Read more
AI app could help diagnose HIV more accurately
Read more
SARS-CoV-2 envelope protein recognition of human cell junction prot…
Read more
COVID-19 dual-antibody therapies effective against variants in anim…
Read more
Dysregulation of brain and choroid plexus cell types in severe COVI…
Read more
Protocols
Single-cell adhesive profil…
By newseditor
Posted 07 May
Parasympathetic neurons der…
By newseditor
Posted 07 May
Non-invasive measurements o…
By newseditor
Posted 05 May
A validation strategy to as…
By newseditor
Posted 04 May
Generation of rat forebrain…
By newseditor
Posted 03 May
Publications
A body-brain circuit that r…
By newseditor
Posted 07 May
Host response during unreso…
By newseditor
Posted 07 May
Sleep pressure modulates si…
By newseditor
Posted 07 May
Reactive oxygen species pro…
By newseditor
Posted 07 May
Mannose controls mesoderm s…
By newseditor
Posted 07 May
Presentations
Hydrogels in Drug Delivery
By newseditor
Posted 12 Apr
Lipids
By newseditor
Posted 31 Dec
Cell biology of carbohydrat…
By newseditor
Posted 29 Nov
RNA interference (RNAi)
By newseditor
Posted 23 Oct
RNA structure and functions
By newseditor
Posted 19 Oct
Posters
A chemical biology/modular…
By newseditor
Posted 22 Aug
Single-molecule covalent ma…
By newseditor
Posted 04 Jul
ASCO-2020-HEALTH SERVICES R…
By newseditor
Posted 23 Mar
ASCO-2020-HEAD AND NECK CANCER
By newseditor
Posted 23 Mar
ASCO-2020-GENITOURINARY CAN…
By newseditor
Posted 23 Mar