Loss of the Actin Remodeler Eps8 Causes Intestinal Defects and Improved Metabolic Status in Mice

In a variety of organisms, including mammals, caloric restriction improves metabolic status and lowers the incidence of chronic-degenerative diseases, ultimately leading to increased lifespan. Here we show that knockout mice for Eps8, a regulator of actin dynamics, display reduced body weight, partial resistance to age- or diet-induced obesity, and overall improved metabolic status. Alteration in the liver gene expression profile, in behavior and metabolism point to a calorie restriction-like phenotype in Eps8 knockout mice. Additionally, and consistent with a calorie restricted metabolism, Eps8 knockout mice show increased lifespan. The metabolic alterations in Eps8 knockout mice correlated with a significant reduction in intestinal fat absorption presumably caused by a 25% reduction in intestinal microvilli length. Our findings implicate actin dynamics as a novel variable in the determination of longevity. Additionally, our observations suggest that subtle differences in energy balance can, over time, significantly affect bodyweight and metabolic status in mice

Neurobeachin, a Regulator of Synaptic Protein Targeting, Is Associated with Body Fat Mass and Feeding Behavior in Mice and Body-Mass Index in Humans

Neurobeachin (Nbea) regulates neuronal membrane protein trafficking and is required for the development and functioning of central and neuromuscular synapses. In homozygous knockout (KO) mice, Nbea deficiency causes perinatal death. Here, we report that heterozygous KO mice haploinsufficient for Nbea have higher body weight due to increased adipose tissue mass. In several feeding paradigms, heterozygous KO mice consumed more food than wild-type (WT) controls, and this consumption was primarily driven by calories rather than palatability. Expression analysis of feeding-related genes in the hypothalamus and brainstem with real-time PCR showed differential expression of a subset of neuropeptide or neuropeptide receptor mRNAs between WT and Nbea+/− mice in the sated state and in response to food deprivation, but not to feeding reward. In humans, we identified two intronic NBEA single-nucleotide polymorphisms (SNPs) that are significantly associated with body-mass index (BMI) in adult and juvenile cohorts. Overall, data obtained in mice and humans suggest that variation of Nbea abundance or activity critically affects body weight, presumably by influencing the activity of feeding-related neural circuits. Our study emphasizes the importance of neural mechanisms in body weight control and points out NBEA as a potential risk gene in human obesity

Carbon and nitrogen turnover during a mesocosm experiment with addition of Palmaria decipiens and Desmarestia anceps to sediments from Potter Cove

To understand the fate of the increasing amount of macroalgal detritus in Antarctic shallow subtidal sediments, a mesocosm experiment was conducted to track 13C and 15N labelled macroalgal detritus into the benthic bacterial, meio- and macrofaunal biomass and respiration of sediments from Potter Cove (King George Island). We compared the degradation pathways of two macroalgae species: one considered palatable for herbivores (the red algae Palmaria decipiens), and one considered non-palatable for herbivores (the brown algae Desmarestia anceps). 15 sediment cores were taken from station Faro at 20m water depth. 13C and 15N labelled macroalgae were added to 10 cores: 5 cores received Desmarestia anceps, 5 cores received Palmaria decipiens. 5 cores did not receive any macroalgae and acted as a control. At different points in time, the cores were closed airtight for a dark incubation of 12h, during which oxygen was measured to calculate Total Oxygen Uptake (TOU), next to 13C-DIC, total nutrients and 15N-labelled nutrients (NH4, NOx and N2). The next day, the cores were sacrificed to determine the assimilation of macroalgae detritus in bacteria, microphytobenthos, meiofauna, macrofauna. Also the remaining large (>1mm) macroalgae fragments were recovered and the bulk POC and PN of the sediment was measured. The sampling points are 1d after addition, and 7, 14 and 21 and 26 days after addition of macroalgae detritus