NAMPT-mediated NAD+ biosynthesis is indispensable for adipose tissue plasticity and development of obesity

Objective: The ability of adipose tissue to expand and contract in response to fluctuations in nutrient availability is essential for the maintenance of whole-body metabolic homeostasis. Given the nutrient scarcity that mammals faced for millions of years, programs involved in this adipose plasticity were likely evolved to be highly efficient in promoting lipid storage. Ironically, this previously advantageous feature may now represent a metabolic liability given the caloric excess of modern society. We speculate that nicotinamide adenine dinucleotide (NAD+) biosynthesis exemplifies this concept. Indeed NAD+/NADH metabolism in fat tissue has been previously linked with obesity, yet whether it plays a causal role in diet-induced adiposity is unknown. Here we investigated how the NAD+ biosynthetic enzyme nicotinamide phosphoribosyltransferase (NAMPT) supports adipose plasticity and the pathological progression to obesity. Methods: We utilized a newly generated Nampt loss-of-function model to investigate the tissue-specific and systemic metabolic consequences of adipose NAD+ deficiency. Energy expenditure, glycemic control, tissue structure, and gene expression were assessed in the contexts of a high dietary fat burden as well as the transition back to normal chow diet. Results: Fat-specific Nampt knockout (FANKO) mice were completely resistant to high fat diet (HFD)-induced obesity. This was driven in part by reduced food intake. Furthermore, HFD-fed FANKO mice were unable to undergo healthy expansion of adipose tissue mass, and adipose depots were rendered fibrotic with markedly reduced mitochondrial respiratory capacity. Yet, surprisingly, HFD-fed FANKO mice exhibited improved glucose tolerance compared to control littermates. Removing the HFD burden largely reversed adipose fibrosis and dysfunction in FANKO animals whereas the improved glucose tolerance persisted. Conclusions: These findings indicate that adipose NAMPT plays an essential role in handling dietary lipid to modulate fat tissue plasticity, food intake, and systemic glucose homeostasis. Keywords: Adipose metabolism, Obesity, NAMPT, NAD+ synthesis, Energy homeostasis, Adipose plasticity, Glucose homeostasi

Intercomparison and Validation of SAR-Based Ice Velocity Measurement Techniques within the Greenland Ice Sheet CCI Project

Ice velocity is one of the products associated with the Ice Sheets Essential Climate Variable. This paper describes the intercomparison and validation of ice-velocity measurements carried out by several international research groups within the European Space Agency Greenland Ice Sheet Climate Change Initiative project, based on space-borne Synthetic Aperture Radar (SAR) data. The goal of this activity was to survey the best SAR-based measurement and error characterization approaches currently in practice. To this end, four experiments were carried out, related to different processing techniques and scenarios, namely differential SAR interferometry, multi aperture SAR interferometry and offset-tracking of incoherent as well as of partially-coherent data. For each task, participants were provided with common datasets covering areas located on the Greenland ice-sheet margin and asked to provide mean velocity maps, quality characterization and a description of processing algorithms and parameters. The results were then intercompared and validated against GPS data, revealing in several cases significant differences in terms of coverage and accuracy. The algorithmic steps and parameters influencing the coverage, accuracy and spatial resolution of the measurements are discussed in detail for each technique, as well as the consistency between quality parameters and validation results. This allows several recommendations to be formulated, in particular concerning procedures which can reduce the impact of analyst decisions, and which are often found to be the cause of sub-optimal algorithm performance