Nonalcoholic fatty liver disease (NAFLD) is a major health problem, and its prevalence has increased in recent years, concurrent with rising rates of obesity and other metabolic diseases. Currently, there are no FDA‐approved pharmacological therapies for NAFLD, and lifestyle interventions, including weight loss and exercise, remain the cornerstones for treatment. Manipulating diet composition and eating patterns may be a sustainable approach to NAFLD treatment. Dietary strategies including Paleolithic, ketogenic, Mediterranean, high‐protein, plant‐based, low‐carbohydrate, and intermittent fasting diets have become increasingly popular because of their purported benefits on metabolic disease. This review highlights what is currently known about these popular dietary approaches in the management of NAFLD in clinical populations with mechanistic insight from animal studies. It also identifies key knowledge gaps to better inform future preclinical and clinical studies aimed at the treatment of NAFLD.

Kindling is a phenomenon of activity-dependent neural circuit plasticity induced by repeated seizures that results in progressive permanent increases in susceptibility to epilepsy. As the permanent structural and functional modifications induced by kindling include a diverse range of molecular, cellular, and functional alterations in neural circuits, it is of interest to determine if genetic background associated with seizure-induced plasticity might also influence plasticity in neural circuitry underlying other behaviors. Outbred Sprague-Dawley (SD) rats were selected and bred for ~15 generations for “fast’ or “slow” rates of kindling development in response to stimulation of the perforant path input to the hippocampus. After 7-8 generations of selection and breeding, consistent phenotypes of “fast” and “slow” kindling rates were observed. By the 15th generation “fast” kindling rats referred to as Perforant Path Kindling Susceptible (PPKS) rats demonstrated a kindling rate of 10.7 ± 1.1 afterdischarges (ADs) to the milestone of the first secondary generalized (Class V) seizure, which differed significantly from “slow” kindling Perforant Path Kindling Resistant (PPKR) rats requiring 25.5 ± 2.0 ADs, and outbred SD rats requiring 16.8 ± 2.5 ADs (p < 0.001, ANOVA). Seizure-naïve adult PPKS and PPKR rats from offspring of this generation and age-matched adult outbred SD rats were compared in validated behavioral measures including the open field test as a measure of exploratory activity, the Morris water maze as a measure of hippocampal spatial memory, and fear conditioning as a behavioral paradigm of associative fear learning. The PPKS (“fast” kindling) strain with increased susceptibility to seizure-induced plasticity demonstrated statistically significant increases in motor exploratory activity in the open field test and reduced spatial learning the Morris water maze, but demonstrated normal fear conditioned learning comparable to outbred SD rats and the “slow” kindling-resistant PPKR strain. These results confirm that selection and breeding on the basis of responses to repeated pathway activation by stimulation can produce enduring modification of genetic background influencing behavior. These observations also suggest that genetic background underlying susceptibility or resistance to seizure-induced plasticity in hippocampal circuitry also differentially influences distinct behaviors and learning that depend on circuitry activated by the kindling selection process, and may have implications for associations between epilepsy, comorbid behavioral conditions, and cognition.

This is the first demonstration of globally reduced ChBF in chronic experimental glaucoma in the nonhuman primate. Both the alteration of mfERG waveform components associated with outer retinal function and the reduction in ChBF were greatest in the macula, suggesting that there may be a spatial colocalization between ChBF and some outer retinal effects in glaucoma.

SUPPLEMENTAL MATERIAL FOR DATA PRESENTED IN SUPPLEMENT Animal care and terminal proceduresFor all animal experiments, room temperature was kept constant at 21-22 degrees Celsius with a 12:12 light/dark cycle. Food intake and body weight of the animals was recorded weekly, and body composition (4in1-1100 Analyzer; EchoMRI, Houston, TX) measured monthly. Food consumption was measured by taking the difference in grams of food given and grams of food remaining 7 days later and multiplying total grams consumed by energy content per gram of the diet (CD -3.5kcal/gram, WD -4.75kcal/gram) and dividing by 7 to give kilocalories per day. On the day of euthanasia, mice were fasted overnight for 12 hr (2000-0800), before being anesthetized with pentobarbital sodium (50 mg/kg). Blood was collected via cardiac puncture, and the animals were euthanized via removal of the heart. Livers were quickly excised from anesthetized mice and prepared for mitochondrial isolation, homogenization for palmitate oxidation, and fixed in 10% formalin or snap-frozen in liquid nitrogen for later processing as described in detail in the following sections. Glucose, insulin, and pyruvate tolerance testingA subset of CD and WD-fed eNOS fl/fl and eNOS hep-/male mice (22-30 weeks of age) were used for glucose, insulin, and pyruvate tolerance tests, to determine the effects of hepatocellular eNOS deficiency on whole body glucose homeostasis. For all testing, mice were fasted in single cages with fresh bedding and ad libitum access to water. For glucose tolerance testing (GTT), mice were fasted overnight prior to baseline testing. At the end of the fast, the tail was nicked and blood sampled via a glucometer (Alpha Trak, Abbott Labs), to determine baseline blood glucose. Mice