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

Early adipogenesis contributes to excess fat accumulation in cave populations of <i>Astyanax mexicanus</i>

Cavefish populations of Astyanax mexicanus have increased body fat compared to surface fish populations of the same species when fed ad libitum in the laboratory. We have previously shown that some cavefish populations display hyperphagia (elevated appetite) to increase food consumption, fat deposition and starvation resistance. However, not all cavefish populations display hyperphagia, yet all previously tested cavefish display elevated body fat levels. Here we have extended this analysis by focusing on visceral fat acquisition in three independently derived cavefish populations. We show that cavefish from two independently derived cavefish populations (Pachón and Tinaja) display increased amounts of visceral adipose tissue (VAT) due to hypertrophy of visceral adipocytes while Molino cavefish display hypertrophy but only slightly elevated VAT levels compared to surface fish. Furthermore, we show that Pachón and Tinaja cavefish develop increased VAT even when food intake is matched to surface fish, suggesting appetite independent mechanisms. We show that in the Pachón population, the differences in the visceral fat in adults correlates with changes in the timing of visceral development, making a developmental contribution likely. Visceral fat development in surface fish starts between 10 and 11 dpf, while in Pachón cavefish, visceral fat cells become visible as early as 8 dpf and develop significantly higher amounts of lipid droplets before surface fish start visceral fat accumulation. We further show that this developmental difference is unique to the Pachón cavefish population, while the Tinaja cavefish population - which displays hyperphagia - starts to develop visceral fat similar to surface fish. We suggest the differences in early adipogenesis in the Pachón population as an additional strategy of increased fat gain in cavefish to adapt to food scarcity

Expert consensus on multidisciplinary therapy of colorectal cancer with lung metastases (2019 edition)

Abstract The lungs are the second most common site of metastasis for colorectal cancer (CRC) after the liver. Rectal cancer is associated with a higher incidence of lung metastases compared to colon cancer. In China, the proportion of rectal cancer cases is around 50%, much higher than that in Western countries (nearly 30%). However, there is no available consensus or guideline focusing on CRC with lung metastases. We conducted an extensive discussion and reached a consensus of management for lung metastases in CRC based on current research reports and the experts’ clinical experiences and knowledge. This consensus provided detailed approaches of diagnosis and differential diagnosis and provided general guidelines for multidisciplinary therapy (MDT) of lung metastases. We also focused on recommendations of MDT management of synchronous lung metastases and initial metachronous lung metastases. This consensus might improve clinical practice of CRC with lung metastases in China and will encourage oncologists to conduct more clinical trials to obtain high-level evidences about managing lung metastases