RIG-I Deficiency Promotes Obesity-Induced Insulin Resistance.
Gabsik YangHye Eun LeeJin Kyung SeokHan Chang KangYong-Yeon ChoHye Suk LeeJoo Young LeePublished in: Pharmaceuticals (Basel, Switzerland) (2021)
Inflammation and immunity are linked to the onset and development of obesity and metabolic disorders. Pattern recognition receptors (PRRs) are key regulators of inflammation and immunity in response to infection and stress, and they have critical roles in metainflammation. In this study, we investigated whether RIG-I (retinoic acid-inducible gene I)-like receptors were involved in the regulation of obesity-induced metabolic stress in RIG-I knockout (KO) mice fed a high-fat diet (HFD). RIG-I KO mice fed an HFD for 12 weeks showed greater body weight gain, higher fat composition, lower lean body mass, and higher epididymal white adipose tissue (eWAT) weight than WT mice fed HFD. In contrast, body weight gain, fat, and lean mass compositions, and eWAT weight of MDA5 (melanoma differentiation-associated protein 5) KO mice fed HFD were similar to those of WT mice fed a normal diet. RIG-I KO mice fed HFD exhibited more severely impaired glucose tolerance and higher HOMA-IR values than WT mice fed HFD. IFN-β expression induced by ER stress inducers, tunicamycin and thapsigargin, was abolished in RIG-I-deficient hepatocytes and macrophages, showing that RIG-I is required for ER stress-induced IFN-β expression. Our results show that RIG-I deficiency promotes obesity and insulin resistance induced by a high-fat diet, presenting a novel role of RIG-I in the development of obesity and metabolic disorders.
Keyphrases
- high fat diet
- insulin resistance
- high fat diet induced
- adipose tissue
- weight gain
- metabolic syndrome
- polycystic ovary syndrome
- skeletal muscle
- body mass index
- weight loss
- type diabetes
- stress induced
- poor prognosis
- physical activity
- immune response
- birth weight
- oxidative stress
- magnetic resonance
- breast cancer cells
- body weight
- magnetic resonance imaging
- case report
- dendritic cells
- high glucose
- high resolution
- gene expression
- long non coding rna
- mass spectrometry
- pi k akt
- single molecule
- liver injury
- diabetic rats
- endothelial cells