Medical Bulletin 25/ July/ 2024

A recent Clinical Nutrition study examined how significant weight loss in highly obese individuals influences their metabolism, psychological state, and decision-making processes.

Research shows that metabolic signals, like blood glucose levels, have been essential for survival, influencing decisions on territory and mating by indicating energy needs. Glucose helps the brain gauge if more resources are required, and mood also affects decision-making.

Emotional eating, aimed at improving mood, often leads to high-calorie food overconsumption and increased obesity risk. Obesity disrupts metabolism and raises blood glucose levels. However, there is limited research on how restoring glucose function and mood might affect decision-making.

The study explored how metabolic and psychological factors affect risky decision-making in obese individuals and examined the impact of weight loss on these decisions. Participants engaged in a computerized gambling task to assess risk propensity, with HbA1c levels and mood measured using the PANAS questionnaire. It was hypothesized that risk-taking would be positively correlated with BMI and that HbA1c would become a stronger predictor of risk propensity after weight loss.

62 obese participants completed a ten-day medically supervised weight loss program, including nutrition counselling and psychotherapy. They made choices between risky options with uncertain rewards and safe options with guaranteed, intermediate rewards. Blood samples, body fat, and weight measurements were recorded at the start and end of the program.

The results showed that weight loss significantly improved both HbA1c levels and mood, making HbA1c a reliable predictor of risk propensity post-weight loss and leading to mood enhancements. HbA1c levels negatively predicted risky decisions, with higher levels associated with lower risk-taking, likely due to perceived high energy availability and a strategy to minimize risk.

Participants were more likely to choose risky options before weight loss, whereas post-intervention, they exhibited reduced risk propensity—a positive behavioural change linked to a healthier lifestyle. Additionally, dopaminergic signalling may influence the relationship between BMI and risk propensity, with lower glucose levels associated with a preference for immediate, smaller rewards over larger, delayed ones.

Risk propensity decreased after weight loss, as demonstrated by individuals who lost weight after participating in a weight management program being more likely to select a safer option than a risky one. These findings indicated that physiological variables like mood could be targeted to prevent individuals from engaging in maladaptive behaviours that lead to weight gain.

Reference: Keweloh, B., Terenzi, D., Froehlich, E., et al. (2024) Weight loss impacts risky decisions in obesity. Clinical Nutrition 43; 1270-1277. doi:10.1016/j.clnu.2024.04.002, https://www.clinicalnutritionjournal.com/article/S0261-5614(24)00108-0/fulltext

Late-life depression, defined as depression onset in individuals over 60, affects up to a third of this age group and can be profoundly debilitating. Recent research highlighted that lifestyle choices may significantly influence the risk of developing this condition. A study conducted by researchers from Mass General Brigham, in collaboration with Yale University, has shown that a higher Brain Care Score (BCS) is associated with a reduced risk of late-life depression.

The findings were published in the journal Frontiers in Psychiatry.

The Brain Care Score (BCS) was previously developed and validated by researchers at Mass General Brigham to help patients and clinicians identify lifestyle changes that could reduce the risk of dementia and stroke. The new study extended the utility of BCS by linking it to a lower risk of late-life depression. This research underscores the shared biological risk factors among stroke, dementia, and depression and highlights the potential of the BCS to guide lifestyle changes for better brain health.

Developed by researchers at the McCance Center and their collaborators, the BCS is designed to help prevent brain diseases by focusing on modifiable risk factors. The score comprises four physical risk factors (blood pressure, haemoglobin A1c, cholesterol, and body mass index), five lifestyle elements (nutrition, alcohol intake, smoking, physical activity, and sleep), and three social/emotional elements (stress, relationships, and life purpose). A higher score on the 21-point scale indicates a lower risk of brain disease.

Utilizing data from over 350,000 participants in the U.K. Biobank (UKB) study, the researchers demonstrated that a five-point increase in baseline BCS was associated with a 33% lower risk of late-life depression and a 27% lower composite risk of late-life depression, stroke, and dementia over a median follow-up period of 13 years.

Under-diagnosis and under-documentation of depression pose challenges to epidemiological research, but the inclusion of primary care records in this study helped mitigate the risk of missing diagnoses. Interestingly, the researchers found a substantial association between baseline BCS and risk of depression in individuals under 50 years of age. While they expected older individuals to show neurodegenerative and inflammatory processes contributing to late-life depression, stroke, and dementia, the neurobiological changes leading to depression in younger individuals are less understood.

Furthermore, the researchers are investigating whether increasing the BCS by five points or more over time can reduce the future risk of stroke and dementia compared to those without significant score increases. The ongoing research aims to elucidate the relationship between BCS scores and the risk of brain diseases.

Reference: Singh, S. D., et al. (2024) The predictive validity of a Brain Care Score for late-life depression and a composite outcome of dementia, stroke, and late-life depression: data from the UK Biobank cohort. Frontiers in Psychiatry. doi.org/10.3389/fpsyt.2024.1373797.

A randomized clinical trial involving obese individuals highlighted the significance of dietary interventions in improving mitochondrial functions and the metabolic profile of monocytes, which are key aspects for controlling chronic inflammation in obesity.

The study was published in the journal Clinical Nutrition.

Various dietary interventions, such as calorie restriction, intermittent fasting, and ketogenic diets, are popular for improving metabolic profiles and promoting weight loss in obese individuals. Mitochondria, essential for cellular energy, adapt to environmental signals to manage energy use. In obesity, mitochondrial dysfunction in monocytes contributes to chronic inflammation, a key feature of obesity. Monocytes regulate fatty acid oxidation to reduce inflammation in low-glucose conditions, suggesting dietary restrictions may impact monocyte bioenergetics.

In the randomized clinical trial, 44 obese individuals were randomly assigned to one of four dietary interventions: calorie restriction, intermittent fasting, a ketogenic diet, or an ad libitum habitual diet for one month. They then received the antibiotic rifaximin while continuing their assigned diets for another month to assess the gut microbiota's role in modulating the diets' effects on mitochondrial function in monocytes. Over four follow-up visits, researchers measured mitochondrial function in monocytes, serum anthropometric and biochemical parameters, and gut microbiota composition in faecal samples.

The results showed that calorie restriction, intermittent fasting, and ketogenic diet significantly increased the maximal respiration oxygen consumption rate in monocytes compared to an ad libitum habitual diet. A significant induction in the gut microbiota diversity was observed in response to both dietary intervention and rifaximin in the intermittent fasting and ketogenic diet groups.

This improved mitochondrial function was linked to reduced monocyte dependence on glycolysis in the intermittent fasting and ketogenic diet groups. These dietary interventions improved body composition and mitochondrial bioenergetic health in obese adults, shifting monocyte energy reliance from glycolysis to mitochondrial respiration. Additionally, positive changes in gut microbiota composition were observed.

The findings suggested that the improvement in mitochondrial function is associated with reduced serum LPS and LPS-mediated intracellular signalling in monocytes.

Reference: Martha Guevara-Cruz. 2024. Intermittent fasting, calorie restriction, and a ketogenic diet improve mitochondrial function by reducing lipopolysaccharide signaling in monocytes during obesity: A randomized clinical trial. Clinical Nutrition. https://www.sciencedirect.com/science/article/pii/S0261561424002280