The study, “Hepatocyte Adenosine Kinase Promotes Excessive Fat Deposition and Liver Inflammation,” appeared in September in the scientific journal Gastroenterology.

Hepatocytes are cells that play pivotal roles in liver function, including in metabolism, detoxification, protein synthesis and innate immunity.

An important player in the proper function of hepatocytes is an enzyme called adenosine kinase, ADK. However, the current study shows that ADK can also drive liver disease progression.

“We aimed to study whether hepatocyte ADK functions to promote excessive fat deposition and liver inflammation,” said Chaodong Wu, M.D., Ph.D., an AgriLife Research Faculty Fellow in the Texas A&M Department of Nutrition. Wu is also a Presidential Impact Fellow of Texas A&M University and the corresponding author for the study.

Wu said NAFLD is highly associated with obesity and progresses to an advanced stage when the liver develops overt inflammatory damage.

This study pointed to the idea that hepatocyte ADK may be an important therapeutic target for managing obesity and NAFLD.

“The research demonstrated that hepatocyte adenosine kinase promotes excessive fat deposition and liver inflammation and is a key factor in the pathogenesis of nonalcoholic fatty liver disease,” he said. “There is already some evidence as to how making dietary changes can be effective in helping prevent or reduce the severity of NAFLD. If further research validates the effects of dietary components on inhibiting adenosine kinase in hepatocytes, scientists could develop new approaches for managing this disease.

About the study

The researchers examined how changes in ADK activity relate to levels of liver inflammation and amount of fat in the liver. The team studied mice that were genetically engineered to have either more or less ADK activity than normal.

The team fed the mice a high-fat diet for 12 weeks or a methionine-choline deficient diet, which is known to contribute to liver injury, for five weeks.

Under these diets, mice with lowered ADK activity in their hepatocytes had lower levels of fat and inflammation in the liver than controls. In contrast, mice with elevated ADK activity had greater body weight and increased body fat, liver fat and liver inflammation levels than normal mice.

Going further, the team conducted experiments to clarify exactly how ADK activity causes these effects.

Wu said the study included the analysis of cell-to-cell crosstalk using single-cell RNA sequencing, which was done with assistance from James Cai, Ph.D., a researcher in Texas A&M’s Department of Veterinary Integrative Biosciences.

“The study’s analysis of lipid profiles in mouse liver samples indicated increased presence of lipids that promote mitochondrial dysfunction, leading in turn to liver inflammation,” Wu said.

The team went on to analyze ADK activity and liver health in human liver samples. Like in mice, the data showed that decreased levels of ADK correlated with lower levels of NAFLD, while increased levels of the enzyme were linked to exacerbated liver steatosis and inflammation. The results also showed that ADK promotes excessive fat deposition and liver inflammation through suppressing fatty acid oxidation in liver cells.

“The amount of hepatocyte ADK protein was positively correlated with the degrees of hepatic steatosis in livers from human subjects,” Wu said. “This novel finding highlights the enzyme’s pathological importance in human NAFLD.”

Diet and NAFLD

A 2020 study by Chaidong Wu, Ph.D., and his team showed that indole, a natural compound found in cruciferous vegetables, may be effective against nonalcoholic fatty liver disease. (Photo courtesy of Texas A&M Department of Horticultural Sciences)

Wu said the new study strongly indicates that an unhealthy diet, such as a diet with enriched saturated fatty acids, has a stimulatory effect on increasing the adenosine kinase protein amount in the liver.

“This, in turn, positively correlates with the degrees of obesity, NAFLD and systemic insulin resistance,” he said.

Wu previously investigated the role of diet in NAFLD in a 2020 study led by AgriLife Research scientists. The study, published in Hepatology, showed that indole — a natural compound found in gut bacteria and cruciferous vegetables such as cabbage, kale, cauliflower and Brussels sprouts — may be effective in fighting the disease.

“This natural compound may lead to new treatments or preventive measures for NAFLD,” Wu said. “Healthy foods with high capacity for indole production are important in preventing NAFLD and are beneficial for improving the health of those with it.”

He said preventing NAFLD’s development and progression may depend on nutritional approaches to ensure that gut microbes allow indole and other metabolites to function effectively.

Because interacting with animals, particularly dogs, is known to help people cope with stress and depression, researchers think that a better understanding of the associated brain activity could help clinicians design improved systems for animal-assisted therapy. The prefrontal cortex might be particularly relevant because it helps regulate and process social and emotional interactions.

In the study, activity in the prefrontal cortex of the brain was non-invasively measured with infrared neuroimaging technology as 19 men and women each viewed a dog, reclined with the same dog against their legs, or petted the dog. Each of these conditions was also performed with Leo, a stuffed lion with fur that was filled with a water bottle to match the temperature and weight of the dogs.

Results showed that prefrontal brain activity was greater when participants interacted with the real dogs, and that this difference was largest for petting, which was the most interactive condition. Another key difference was that prefrontal brain activity increased each time people interacted with the real dog. This was not observed with successive interactions with the stuffed lion, indicating that the response might be related to familiarity or social bonding.

Future studies will be needed to examine the issue of familiarity in detail and whether petting animals can trigger a similar boost of prefrontal brain activity in patients with socioemotional deficits.

The authors add: “The present study demonstrates that prefrontal brain activity in healthy subjects increased with a rise in interactional closeness with a dog or a plush animal, but especially in contact with the dog the activation is stronger. This indicates that interactions with a dog might activate more attentional processes and elicit stronger emotional arousal than comparable nonliving stimuli.”

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For many students, college is a major transition that can facilitate either psychological growth or maladaptive behaviors and psychological problems. Previous studies have found an association between FoMO and disruptive/harmful social media use. A greater understanding of how FoMO influences individual behavior is important to reducing FoMO’s negative influence.

For the new study, 472 college students completed a hard copy questionnaire packet assessing FoMO levels, unethical and illegal behavior while in college, and demographic variables. The researchers analyzed this data both by using standard statistical approaches and by applying a supervised machine learning approach.

With the first analysis approach, the team discovered associations between FoMO and nearly all the behaviors they examined. Higher levels of FoMO were found to be correlated with higher rates of classroom incivility (p<0.001), plagiarism (p=0.003), greater weekly alcohol consumption (p<0.001), lower age when beginning drinking alcohol, increased use of cannabis (p=0.007), stimulants (p<0.001), depressants (p<0.001) and hallucinogens, as well as illegal activities including giving away drugs (p<0.001) and stealing (p<0.001). The machine learning algorithm found similar associations and highlighted the modifying effect of living situation, socioeconomic status and gender on several of the relationships.

The authors suggest that brief FoMO assessments, including just 10 questions, may be valuable risk prediction tools for counselors focused on assisting students in the transition to college or university.

The authors add: “Using Fear of Missing Out (FoMO) and demographic information, we were able to predict class membership (offender/user vs non-offender/non-user) of college students across multiple domains (alcohol and drug use, academic misconduct, illegal behavior) well above baseline (e.g., 50% at baseline vs 87% for academic misconduct). These results suggest that FoMO exists not just as an aversive phenomenon, but it also leads to concrete consequences for individuals and society.”

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