Retinoic acid receptor responder 1 (RARRES1) is silenced in many cancers and is differentially expressed in metabolism associated diseases, such as hepatic steatosis, hyperinsulinemia and obesity. Here we report a novel function of RARRES1 in metabolic reprogramming of epithelial cells. Using non-targeted LC-MS, we discovered that RARRES1 depletion in epithelial cells caused a global increase in lipid synthesis. RARRES1-depleted cells rewire glucose metabolism by switching from aerobic glycolysis to glucose-dependent de novo lipogenesis (DNL). Treatment with fatty acid synthase (FASN) inhibitor, C75, reversed the effects of RARRES1 depletion. The increased DNL in RARRES1-depleted normal breast and prostate epithelial cells proved advantageous to the cells during starvation, as the increase in fatty acid availability lead to more oxidized fatty acids (FAO), which were used for mitochondrial respiration. Expression of RARRES1 in several common solid tumors is also contextually correlated with expression of fatty acid metabolism genes and fatty acid-regulated transcription factors. Pathway enrichment analysis led us to determine that RARRES1 is regulated by peroxisome proliferating activated receptor (PPAR) signaling. These findings open up a new avenue for metabolic reprogramming and identify RARRES1 as a potential target for cancers and other diseases with impaired fatty acid metabolism.
Restoration of foundation species promises to reverse environmental degradation and return lost ecosystem services, but a lack of standardized evaluation across projects limits understanding of recovery, especially in marine systems. Oyster reefs are restored to reverse massive global declines and reclaim valuable ecosystem services, but the success of these projects has not been systematically and comprehensively quantified. We synthesized data on ecosystem services associated with oyster restoration from 245 pairs of restored and degraded reefs and 136 pairs of restored and reference reefs across 3500 km of U.S. Gulf of Mexico and Atlantic coastlines. On average, restoration was associated with a 21‐fold increase in oyster production (mean log response ratio = 3.08 [95% confidence interval: 2.58–3.58]), 34–97% enhancement of habitat provisioning (mean community abundance = 0.51 [0.41–0.61], mean richness = 0.29 [0.19–0.39], and mean biomass = 0.69 [0.39–0.99]), 54% more nitrogen removal (mean = 0.43 [0.13–0.73]), and 89–95% greater sediment nutrients (mean = 0.67 [0.27–1.07]) and organic matter (mean = 0.64 [0.44–0.84]) relative to degraded habitats. Moreover, restored reefs matched reference reefs for these ecosystem services. Our results support the continued and expanded use of oyster restoration to enhance ecosystem services of degraded coastal systems and match many functions provided by reference reefs.
Blue crabs (Callinectes sapidus) are highly mobile, ecologically-important mesopredators that support multimillion-dollar fisheries along the western Atlantic Ocean. Understanding how blue crabs respond to coastal landscape change is integral to conservation and management, but such insights have been limited to a narrow range of habitats and spatial scales. We examined how local-scale to landscape-scale habitat characteristics and bathymetric features (channels and oceanic inlets) affect the relative abundance (catch per unit effort, CPUE) of adult blue crabs across a > 33 km2 seagrass landscape in coastal Virginia, USA. We found that crab CPUE was 1.7 × higher in sparse (versus dense) seagrass, 2.4 × higher at sites farther from (versus nearer to) salt marshes, and unaffected by proximity to oyster reefs. The probability that a trapped crab was female was 5.1 × higher in sparse seagrass and 8 × higher near deep channels. The probability of a female crab being gravid was 2.8 × higher near seagrass meadow edges and 3.3 × higher near deep channels. Moreover, the likelihood of a gravid female having mature eggs was 16 × greater in sparse seagrass and 32 × greater near oceanic inlets. Overall, we discovered that adult blue crab CPUE is influenced by seagrass, salt marsh, and bathymetric features on scales from meters to kilometers, and that habitat associations depend on sex and reproductive stage. Hence, accelerating changes to coastal geomorphology and vegetation will likely alter the abundance and distribution of adult blue crabs, challenging marine spatial planning and ecosystem-based fisheries management.
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