Abstract
Niacin has long been considered as a high-potency drug for beneficially treating lipid abnormalities, however, its anti-atherosclerotic effects have been challenged by recent studies. Here, we demonstrated that oral supplementation of niacin resulted in a significant reduction in body weight and fat mass without affecting food intake in high-fat diet-fed wild-type mice, but not in GPR109A-defeicient mice. Further investigation showed that niacin challenge led to a remarkable inhibition of hepatic lipogenesis via a GPR109A-dependent ERK1/2/AMPK pathway. Additionally, we demonstrated that niacin treatment stimulated thermogenesis in brown adipose tissue by induction of thermogenic genes via GPR109A. Moreover, we observed that mice exposed to niacin exhibited a dramatic decrease in intestinal absorption of fatty acids. Together, our data demonstrate that acting on GPR109A, niacin shows the potential to maintain energy homeostasis by fine-tuning hepatic lipogenesis, BAT/beige thermogenesis and intestinal fat absorption, representing a potential approach to the treatment of lipid abnormalities.
- Abrreviations
- NA
- nicotinic acid;
- HFD
- high fat diet;
- NCD
- normal chow diet;
- TG
- triglyceride;
- TC
- total cholesterol;
- FFA
- free fatty acid;
- LDL
- low-density lipoprotein;
- HDL
- high density lipoprotein;
- WAT
- white adipose tissue;
- eWAT
- epididymal white adipose tissue;
- pWAT
- perirenal white adipose tissue;
- iWAT
- inguinal white adipose tissue;
- sWAT
- subcutaneous white adipose tissue;
- BAT
- brown adipose tissue;
- ITT
- insulin tolerance test;
- GTT
- glucose tolerance test;
- PDH
- pyruvate dehydrogenase;
- ACC
- acetyl CoA carboxylase;
- ACC1
- acetyl CoA carboxylase 1;
- DGAT2
- diacylglycerol acyltransferase 2;
- FAS
- fatty acid synthase;
- SREBP-1c
- sterol regulatory element-binding transcription factor 1;
- SCD-1
- stearoyl-CoA desaturases-1;
- FATP4
- fatty acid transport protein 4;
- I-FABP
- intestinal-type fatty acid-binding protein;
- NPC1L1
- Niemann-Pick C1-Like 1;
- UCP1
- uncoupling protein 1;
- PGC-1α
- peroxisome proliferator-activated receptor gamma coactivator 1-alpha;
- PRDM16
- PR domain containing 16;
- AUC
- area under the curves;