Cracking the obesity code: The protein leverage hypothesis

According to the World Health Organization (WHO), obesity remains a significant threat to global public health. Excess body fat accumulates when more energy is consumed than is burnt; however, there remains a lack of research on the mechanism responsible for this energy imbalance.

In a recent study published in Philosophical Transactions of the Royal Society B, researchers discuss the protein leverage hypothesis (PLH) as an approach to understanding the underlying causes of obesity.

The main aim of this paper was to advocate for more extensive adoption of integrative approaches that consider the reality and complexities of obesity research, including the molecular, behavioral, cultural, and geopolitical influences across the globe. Moreover, the researchers present an integrative framework developed from nutritional ecology, ecological sciences, and nutritional geometry and illustrate how these are applied to examine the underlying causes of obesity.

Study: Protein appetite as an integrator in the obesity system: the protein leverage hypothesis. Image Credit: Lightspring / Shutterstock.com

Nutritional geometry

Nutritional ecology combines nutritional and ecological sciences, focusing on the interplay between nutrition and biology in humans and animals. Comparatively, nutritional geometry is an analytical framework that examines how nutrition and biology intersect in food environments.

Using multi-dimensional geometric representations, nutritional geometry analyzes the interactive and individual effects of dietary components. This framework can also incorporate adjunct variables, thus making it ideal for the development of integrative models that study nutrient interactions and their relationship with biological and environmental factors.

Protein and obesity

Despite the increasing prevalence of obesity in humans due to excess energy intake in the form of fats and carbohydrates, protein consumption has remained stable. The integrative systems perspective suggests that protein dilution by energy-dense carbohydrates and fats can lead to increased food intake and excess calories, contributing to obesity.

Nutrient-specific appetites include appetites for protein, fat, carbohydrates, and minerals such as sodium and calcium. These specific appetites have been observed in many organisms, thus indicating that the specificity is widespread in nature.

Although the behavioral aspects of protein-specific appetites are well-documented, researchers are still studying the underlying mechanisms of protein intake regulation, including neural pathways, sensory modulation, and endocrine signals like fibroblast growth factor 21 (FGF21).

Three randomized control trials (RCTs) have investigated protein prioritization as a mechanism for influencing human energy intake. These trials indicated that increasing dietary protein proportions from 10% to 30% of the total energy intake significantly impacted energy consumption. Thus, protein leverage occurs within this 10-30% range, with less than 10% protein inadequate for regulating energy intake.

Another essential aspect of studying protein leverage in energy consumption is analyzing how ecological variation in the proportion of protein-derived energy relates to actual energy intake in the real world. Several studies, including large RCTs, longitudinal trend analyses, and population-based data, have provided ecological evidence for PLH, with many of them showing an inverse relationship between energy intake and dietary protein content. This was more so in the 10-30% protein range, which supports the concept of protein leverage.

Studies on protein dilution

Several ecological studies have investigated the causes of protein dilution in diets and its connection to increased energy intake. To this end, consuming ultra-processed foods (UPFs) is directly linked to the dietary protein dilution with carbohydrates and fats, which leads to higher total energy intake.

In one study comparing ultra-processed and whole-food diets, researchers demonstrated that protein leverage may have a role in increased calorie intake when subjects choose tasty and lower-protein UPFs. Thus, certain factors like convenience, marketing, cost, and palatability of UPFs may contribute to their over-consumption, which highlights the need to examine why UPFs are preferred over healthier food alternatives.

Integrative models in protein leverage theory provide a framework to study unexplained dietary protein-related phenomena and energy requirements and expenditures. These models suggest that disproportionate increases in protein as compared to non-protein energy requirements may lead to age-related weight gain, susceptibility to obesity, and difficulty maintaining weight loss.

Factors like insulin resistance, lifestyle transitions, metabolic changes, early-life diet, genetic variations, and gut microbiota can influence protein leverage and, as a result, individual- and population-level changes in obesity risk.

Conclusions

Obesity is a complex condition influenced by interactions between several factors, such as psychology, biology, and food environments. This comprehensive review presents an integrative obesity model that highlights the role of protein deficiency and amino acid imbalances in triggering protein-seeking behaviors through increased protein appetite.

The model described in this study emphasizes the importance of considering societal and environmental factors in understanding and addressing the obesity epidemic. Moreover, it underscores the need for a wholesome perspective to identify sustainable intervention points for managing obesity and associated complications.

Written by

Susha Cheriyedath

Susha has a Bachelor of Science (B.Sc.) degree in Chemistry and Master of Science (M.Sc) degree in Biochemistry from the University of Calicut, India. She always had a keen interest in medical and health science. As part of her masters degree, she specialized in Biochemistry, with an emphasis on Microbiology, Physiology, Biotechnology, and Nutrition. In her spare time, she loves to cook up a storm in the kitchen with her super-messy baking experiments.