SR-BI as a target of natural products and its significance in cancer

Scavenger receptor class B type I (SR-BI) protein is an integral membrane glycoprotein. SR-BI is emerging as a multifunctional protein, which regulates autophagy, efferocytosis, cell survival and inflammation. It is well known that SR-BI plays a critical role in lipoprotein metabolism by mediating cholesteryl esters selective uptake and the bi-directional flux of free cholesterol. Recently, SR-BI has also been identified as a potential marker for cancer diagnosis, prognosis, or even a treatment target. Natural products are a promising source for the discovery of new drug leads. Multiple natural products were identified to regulate SR-BI protein expression. There are still a number of challenges in modulating SR-BI expression in cancer and in using natural products for modulation of such protein expression. In this review, our purpose is to discuss the relationship between SR-BI protein and cancer, and the molecular mechanisms regulating SR-BI expression, as well as to provide an overview of natural products that regulate SR-BI expression

How Cavefish Gain High Body Fat to Adapt to Food Scarcity

Food availability variation is a major challenge for some animals in their natural environment. A classic example of food scarcity environment are caves, which lack internal food chains based on photosynthesis. Cavefish populations can gain high body fat to deal with food scarcity, but the underlying mechanisms remain unclear. Here, we used Mexican tetra, Astyanax mexicanus, to address this question. To this end, I interrogated two perspectives: adipocyte development and lipid metabolism. I showed that cavefish populations store large amounts of fat in different regions throughout the body when fed ad libitum in the lab. After paired feeding, I found Tinaja and Pachón cavefish populations still have more visceral fat than surface fish, while maintaining similar body weight. This is largely because of hypertrophy of adipocytes in cavefish populations. Moreover, I found Pachón cavefish can develop their adipocytes earlier and faster than surface fish, providing a developmental mechanism for high body fat accumulation. I also found that high body fat is in part due to higher expression of de novo lipogenesis genes in cavefish livers compared to surface fish after paired feeding. The fatty acid profiling of the liver also indicated enhanced lipogenesis in cavefish. Moreover, the lipid metabolism regulator, Peroxisome proliferator-activated receptor γ (Pparγ), was upregulated at both transcript and protein levels in cavefish livers. Chromatin immunoprecipitation sequencing (ChIP-seq) showed that Pparγ binds cavefish promoter regions of genes to a higher extent than surface fish. Using pharmacology in Astyanax, I showed that inhibiting Pparγ slowed down the fat accumulation, indicating upregulation Pparγ contributes to fat accumulation. Finally, I identified nonsense mutations in per2, a known repressor of Pparγ. Taken together, this study reveals that upregulated Pparγ promotes higher levels of lipogenesis in the liver and contributes to higher body fat of cavefish to adapt to nutrient limited environments