Biology subjects

Maxwell, B. A.

Publications and source records attributed to Maxwell, B. A..

3 recordsLinked to original sources

bioRxiv2026

A Regionally Inspired West Virginia Obesogenic Diet Induces Fat Accretion and Metabolic Dysfunction While Identifying Sex Disparity

Obesity prevalence continues to rise in the United States, with a disproportionate burden falling to West Virginia. To investigate the metabolic effects of region-specific dietary patterns, we developed the West Virginia Obesogenic Diet (WV-OD), a compositionally defined rodent diet based on nutritional analyses of meals consumed by obese individuals in the state. The WV-OD closely mirrors the macronutrient profile of the average American diet while incorporating regional features such as a greater sodium level and significantly less fiber. We compared the metabolic effects of the WV-OD to a matched control diet (WV-CD) and to a widely used high-fat diet (HFD, 60% of calories derived from fat) in male and female C57BL/6J mice. After 19 weeks, WV-OD-fed males exhibited weight gain and adiposity comparable to HFD-fed counterparts, along with glucose intolerance and hepatic triglyceride accumulation confirming the obesogenic and metabolically disruptive properties of the WV-OD. Unlike HFD-fed mice, WV-OD-fed males also displayed elevated circulating cholesterol and cholesterol esters without corresponding increases in hepatic total cholesterol. When compared to the HFD, the WV-OD did not increase uric acid or xanthine oxidoreductase (XOR) content of liver or circulation; however, both males and females on the WV-OD demonstrated trends towards elevated plasma uric acid. Interestingly, while exhibiting a similar caloric intake on either diet, the WV-OD females did not demonstrate significant fat accretion or metabolic dysfunction compared to females subjected to the 60% HFD. In toto, these findings: 1) establish the WV-OD as a regionally-grounded, yet broadly representative tool for modeling diet-induced obesity and metabolic dysfunction, 2) offer a physiologically relevant alternative to extreme-fat dietary models in preclinical research and 3) highlight sex-based differences in response to diet-induced obesity.

physiology↗

bioRxiv2021

Ubiquitination of G3BP1 mediates stress granule disassembly in a stress-specific manner

Stress granules are dynamic, reversible condensates composed of RNA and protein that assemble in response to a variety of stressors and are normally disassembled after stress is removed. Whereas the composition of stress granules and the mechanisms underlying their assembly have been extensively studied, far less is known about the mechanisms that govern disassembly. Impaired disassembly has been implicated in some diseases. Here we report that stress granule disassembly is context-dependent and, in the setting of heat shock, requires ubiquitination of G3BP1, the central protein within the stress granule RNA-protein network. Ubiquitinated G3BP1 interacts with the ER-resident protein FAF2, which engages the ubiquitin-dependent segregase p97/VCP. Targeting G3BP1 enables the stress granule-specific interaction network to fall below the percolation threshold for phase separation, which causes disassembly. One Sentence SummaryUbiquitination of G3BP1 mediates FAF2- and p97/VCP-dependent disassembly of heat-induced stress granules

cell biology↗

bioRxiv2021

Ubiquitination is essential for recovery of cellular activities followingheat shock

Eukaryotic cells respond to stress via adaptive programs that include reversible shutdown of key cellular processes, the formation of stress granules, and a global increase in ubiquitination. The primary function of this ubiquitination is generally considered to be tagging damaged or misfolded proteins for degradation. Here we show that different types of stress generate distinct ubiquitination patterns. For heat stress, ubiquitination correlates with cellular activities that are downregulated during stress, including nucleocytoplasmic transport and translation, as well as with stress granule constituents. Ubiquitination is not required for the shutdown of these processes or for stress granule formation, but is essential for resumption of cellular activities and for stress granule disassembly. These findings indicate that stress-induced ubiquitination primes the cell for recovery following heat stress. One Sentence SummaryStress-induced ubiquitination is essential for recovery of cellular activities following heat stress.

cell biology↗