Gene P. Ables, Ph.D.

Our studies have demonstrated that a sulfur amino acid-restricted (SAAR) diet protects mice against fatty liver disease, obesity, and diabetes, does not affect cardiac function, and attenuates kidney injury, but reduces bone mass (Ables et al., 2015; Ables et al., 2012; Cooke et al., 2020; Cooke et al., 2018; Ouattara et al., 2016). Compared to their control-fed (CF) counterparts, the circulating profile of SAAR rodents indicates reduced glucose, insulin, IGF-1, and leptin, while adiponectin and FGF21 are elevated (Ables et al., 2015; Cooke et al., 2020; Malloy et al., 2006). In addition, we have also identified the molecular mechanisms by which a SAAR diet confers protection in the age-related disease models we have tested. For example, protection against fatty liver disease in mice fed a high-fat SAAR diet could be explained by upregulated glucose-sensitizing hepatic Pparg and Fgf21 genes and downregulated Scd1 gene (Ables et al., 2012). In addition, SAAR attenuated kidney injury in mice by downregulating renal genes that are involved during inflammation and fibrosis, such as Tnfa and Fn1, respectively (Cooke et al., 2018). Most recently, we demonstrated that reduced adipose tissue mass in obese mice activate autophagy independent of the actions of adiponectin and FGF21 (Cooke et al., 2020).

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Dr. Ables continues to investigate the effects of SAAR on neurodegenerative diseases using a mouse model for amyotrophic lateral sclerosis amyotrophic lateral sclerosis (ALS), commonly known as Lou Gehrig’s disease. ALS is a progressive and fatal neuromuscular disease characterized by neuroinflammation progressing to neurodegeneration. No cure for ALS has yet been identified, and there is a dearth of proven useful therapeutic interventions. One of the causes of neuronal death in ALS is oxidative damage, something SAAR in rodents has shown to beneficially effect. However, the effect of SAAR on neurological systems using a mouse disease model such as ALS has not yet been examined. To investigate this, Dr. Ables’s lab is conducting experiments on transgenic mice transfected with the ALS-associated G93A human superoxide dismutase 1 mutation, SOD1-G93A. They are in the process of analyzing data on the mechanisms by which SAAR effects the onset of disease, measured by various strength and agility tests. They are also analyzing whether SAAR suppresses disease progression by attenuation of inflammation and oxidative stress markers in neurons and muscle cells. Characterization of the effects of SAAR in SOD1-G93A mice is the first step that will direct future investigations of how SAAR may affect other neurological diseases.