Medical Bulletin 09/ May/ 2024

In a study published in the journal Cell Metabolism, researchers from the German Cancer Research Center (DKFZ) and the University of Tübingen showed that intermittent fasting on a 5:2 schedule can halt the development of liver inflammation and liver cancer caused by fatty liver disease.

The most prevalent chronic liver condition is non-alcoholic fatty liver disease (NAFLD), which can lead to serious complications such as liver inflammation (metabolic dysfunction-associated steatohepatitis, or NASH), liver cirrhosis, and even liver cancer if left untreated. Non-alcoholic fatty liver disease is primarily associated with obesity, which is on the rise globally. Consequently, affected countries are witnessing a sharp increase in cases of liver failure and liver cancer.

Intermittent fasting has been shown in several studies to be an effective means of reducing weight and alleviating certain metabolic disorders. During fasting periods, the body undergoes autophagy, a cellular process that removes damaged components and promotes cellular repair. Intermittent fasting also improves insulin sensitivity, lowers inflammation, and enhances fat burning.

In the study, mice were fed a high-sugar and high-fat diet resembling the typical Western diet. One group had constant access to food, leading to weight gain and chronic liver inflammation. The other group practiced 5:2 intermittent fasting, where they ate normally for five days but fasted for two days each week. This intermittent fasting regimen aimed to assess its potential to protect the liver from fatty degeneration and chronic inflammation.

The results showed that despite consuming a high-calorie diet, the mice practicing intermittent fasting did not gain weight, showed fewer signs of liver disease, and had lower levels of biomarkers indicating liver damage. This resistance to fatty liver development was independent of total calorie intake, as the mice compensated for lost rations after fasting periods.

The findings revealed that the number and duration of fasting cycles, as well as the timing of the fasting phase, influenced protection against liver inflammation. A 5:2 dietary pattern and 24-hour fasting phases were more effective than other variants, especially with particularly unhealthy diets requiring more frequent fasting cycles.

Reference: Suchira Gallage, Mathias Heikenwalder, et al; A 5:2 intermittent fasting regimen ameliorates NASH and fibrosis and blunts HCC development via hepatic PPARα and PCK1; Cell Metabolism,2024; https://doi.org/10.1016/j.cmet.2024.04.015.

In a study from University of Colorado Department of Medicine, researchers investigated whether adequate sleep can help prevent osteoporosis.

Osteoporosis is a condition characterized by weakening bones, making them fragile and more prone to fractures. Factors such as aging, hormonal changes, inadequate calcium and vitamin D intake, lack of physical activity, and certain medications can increase the risk of developing osteoporosis.

In their early to mid-20s, individuals reach peak bone mineral density, which is higher in men than in women and influences fracture risk later in life. Bone density remains stable for decades after this peak but declines during menopause for women and with age for men. Aging also alters sleep patterns, reducing total sleep time and increasing sleep latency. Additionally, deep restorative sleep, called slow wave sleep, decreases with age.

“Genes regulating our internal clock exist in all bone cells. When these cells form or break down bone, they release substances into the blood, indicating bone turnover. These markers follow a daily rhythm, with bone resorption markers showing a larger amplitude than bone formation markers. This rhythmicity likely plays a crucial role in bone metabolism, implying that disruptions in sleep and circadian rhythms may directly impact bone health,” said Christine Swanson, an associate professor in the Division of Endocrinology, Metabolism, and Diabetes.

In this study, participants were placed in a controlled inpatient environment where they lived on a 28-hour schedule instead of the typical 24-hour day. Bone turnover markers were measured before and after the intervention, revealing significant negative effects on bone turnover.

Both men and women experienced declines in markers of bone formation, with younger individuals showing greater declines compared to older individuals. In addition, young women showed significant increase in the bone resorption marker.

“If a person is forming less bone while still resorbing the same amount — or even more — then, over time, that could lead to bone loss, osteoporosis, and increased fracture risk. And sex and age may play an important role, with younger women potentially being the most susceptible to the detrimental impact of poor sleep on bone health,” said Swanson.

Reference: Christine Swanson, MD, MCR; Could Getting Enough Sleep Help Prevent Osteoporosis? May 2024; UNIVERSITY OF COLORADO ANSCHUTZ MEDICAL CAMPUS

In a study published in The American Journal of Gastroenterology, researchers examined the variation in small bowel microbiome profiles between obese individuals and those of normal weight.

Obesity is associated with increased risks of a wide variety of diseases, including cardiovascular diseases, metabolic syndrome and type 2 diabetes (T2D), and certain cancers. Worldwide, obesity contributes to an estimated 2.8 million deaths annually.

Imbalances in gut microbial populations have repeatedly been reported in patients with obesity-related diseases. Recent research has indicated that individuals with lower bacterial richness and gene content tend to have a higher inflammatory phenotype, along with conditions like obesity and insulin resistance. Little is known about differences in the small bowel microbiome between obese and non-obese individuals, despite previous research. Understanding this link is vital for understanding the gut microbiome's role in obesity and developing targeted interventions.

In the study, subjects aged 18-80, undergoing upper endoscopy were categorized by BMI: normal weight (BMI 18.5-24.9), overweight (BMI 25-29.9), and obese (BMI >30), following Centers for Disease Control and Prevention guidelines. A post-screening step excluded those with diabetes, gastric bypass history, weight control medication use, or recent antibiotics. Samples were collected from duodenal aspirates and serum, along with assessments of microbial metabolic functions and serum biomarkers.

Direct analysis of the duodenal microbiome identified key genera associated with overweight and obesity, including some previously identified in stool, e.g., Bifidobacterium and Lactobacillus. Specific species and strains that exhibit differing associations with overweight and obesity were also identified.

The findings revealed microbial species associated with overweight and obesity. "Escalation" features from normal weight to obesity included reduced Bacteroides pyogenes and Staphylococcus hominis, and decreased biogenic amine metabolism potential. "De-escalation" features from normal weight to overweight and overweight to obesity involved changes in Lactobacillus acidophilus, Lactobacillus hominis, and Bifidobacterium dentium, potentially impacting obesity.

"We identify small bowel microbial species associated with overweight and obesity, as well as escalation and de-escalation features that could potentially be selected as therapeutic targets. These findings illustrate that, although stool studies can and have provided very valuable data, direct analysis of the small bowel has yielded specific targets for further study," said the authors.

Reference: Leite, Gabriela PhD; Barlow, Gillian M. PhD; Characterization of the Small Bowel Microbiome Reveals Different Profiles in Human Subjects Who Are Overweight or Have Obesity. The American Journal of Gastroenterology ():10.14309/ajg.0000000000002790, April 22, 2024. | DOI: 10.14309/ajg.0000000000002790