How do we get fat? An epidemiologic and metabolic approach

Area of Science:

• Physiology
• Genetics
• Molecular Biology

Background:

• Obesity is a complex condition arising from a sustained imbalance between energy intake and expenditure.
• The first law of thermodynamics explains energy balance but not the physiological dysregulation leading to obesity.
• Recent decades have seen significant advancements in understanding the molecular and physiological underpinnings of body fat regulation.

Purpose of the Study:

• To review the expansion of knowledge regarding physiological and molecular mechanisms regulating body fat.
• To highlight the impact of cloning genes for mouse monogenic obesity syndromes and their human counterparts.
• To discuss the role of molecular and reverse genetic studies in identifying critical pathways for body fat and food intake regulation.

Main Methods:

• Review of research over the past two decades focusing on obesity mechanisms.
• Cloning of genes associated with five mouse monogenic obesity syndromes.
• Characterization of human counterparts to these mouse syndromes.
• Conducting extensive molecular and reverse genetic studies, including mouse knockouts.

Main Results:

• Cloning of genes for five mouse monogenic obesity syndromes has been impactful.
• Identification and characterization of human counterparts to these syndromes.
• Molecular and reverse genetic studies have established critical pathways regulating body fat and food intake.
• These studies have validated or refuted the importance of previously identified pathways.

Conclusions:

• Advances in molecular genetics have greatly expanded our understanding of obesity.
• Gene cloning and genetic studies are crucial for elucidating the complex regulatory pathways of body fat and food intake.
• Further research continues to refine our knowledge of obesity's physiological and molecular basis.