Top 3 Biorxiv Papers Today in Physiology


1.997 Mikeys
#1. A big-data approach to understanding metabolic rate and response to obesity in laboratory mice
June K Corrigan, Deepti Ramachandran, Yuchen He, Colin Palmer, Michael J Jurczak, Bingshan Li, Randall H Friedline, Jason K Kim, Jon J Ramsey, Louise Lantier, Owen P McGuinness, Alexander S Banks, Mouse Metabolic Phenotyping Center Energy Balance Working Group
Maintaining a healthy body weight requires an exquisite balance between energy intake and energy expenditure. In humans and in laboratory mice these factors are experimentally measured by powerful and sensitive indirect calorimetry devices. To understand the genetic and environmental factors that contribute to the regulation of body weight, an important first step is to establish the normal range of metabolic values and primary sources contributing to variability in results. Here we examine indirect calorimetry results from two experimental mouse projects, the Mouse Metabolic Phenotyping Centers and International Mouse Phenotyping Consortium to develop insights into large-scale trends in mammalian metabolism. Analysis of nearly 10,000 wildtype mice revealed that the largest experimental variances are consequences of institutional site. This institutional effect on variation eclipsed those of housing temperature, body mass, locomotor activity, sex, or season. We do not find support for the claim that female mice have greater...
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1.994 Mikeys
#2. Divergent Energy Expenditure Impacts Mouse Metabolic Adaptation to Acute High-Fat/High-Sucrose Diet Producing Sexually Dimorphic Weight Gain Patterns
E. Matthew M Morris, Roberto D. Noland, Julie A. Allen, Colin S. McCoin, Qing Xia, Devin C. Koestler, Robin P. Shook, John R.B. Lighton, Julie A Christianson, John P. Thyfault
Objective: Long-term weight gain can result from cumulative small weight increases due to short-term excess caloric intake during weekends and holidays. Increased physical activity may mediate weight gain through increases in energy expenditure (EE) and reductions in energy balance. Current methods for modulating mouse EE (e.g. − exercise, chemical uncouplers, etc.) have confounding effects. However, it is known that mouse EE linearly increases as housing temperature decreases below the thermoneutral zone. Methods: To determine how robust differences in baseline EE impact 7-day changes in weight and body composition on low-fat and high-fat, high-sucrose (HFHS) diets, we performed indirect calorimetry measurements in male and female mice housed at divergent temperatures (20°C vs. 30°C). Results: As expected, mice housed at 30°C have ~40% lower total EE and energy intake compared to 20°C mice regardless of diet or sex. Energy balance was increased with HFHS in all groups, with ~30% greater increases observed in 30°C versus 20°C...
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1.99 Mikeys
#3. Chemical genetics strategy to profile kinase target engagement reveals role of FES in neutrophil phagocytosis via SYK activation
Tom van der Wel, Riet Hilhorst, Hans den Dulk, Tim van den Hooven, Nienke M. Prins, Joost A.P.M. Wijnakker, Bogdan I. Florea, Eelke B. Lenselink, Gerard J.P. van Westen, Rob Ruijtenbeek, Herman S. Overkleeft, Allard Kaptein, Tjeerd Barf, Mario van der Stelt
Chemical tools and methods that report on target engagement of endogenously expressed protein kinases by small molecules in human cells are highly desirable. Here, we describe a chemical genetics strategy that allows the study of non-receptor tyrosine kinase FES, a promising therapeutic target for cancer and immune disorders. Precise gene editing was used in combination with a rationally designed, complementary fluorescent probe to visualize endogenous FES kinase in HL-60 cells. We replaced a single oxygen atom by a sulphur in a serine residue at the DFG-1 position of the ATP-binding pocket in an endogenously expressed kinase, thereby sensitizing the engineered protein towards covalent labeling and inactivation by a fluorescent probe. The temporal control offered by this strategy allows acute inactivation of FES activity both during myeloid differentiation and in terminally differentiated neutrophils. Our results show that FES activity is dispensable for differentiation of HL-60 cells towards macrophages. Instead, FES plays a key...
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Total Words: 14679
Unqiue Words: 3726

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