Obesity and leptin resistance

In search for the causes of obesity, I came across this wonderful lecture by Stephan Guyenet on What causes leptin resistance? as shown below. Stephan is an obesity researcher and neurobiologist. His blog Whole Health Source is full of useful information on obesity and nutrition.

This video contains technical terms on cell signaling pathway and biochemical research. If you have some training in these fields, please watch the video. If you find it difficult to understand, I have summarized the main information in plain language below.

Leptin is the satiety hormone that prevents you from getting fat. When your adipose tissue (the fat cells) stores up fat, it secrets leptin. Leptin travels up to your brain and your brain will tell you to eat less and spend more energy, and thus to reduce fat in your body. As illustrated in the graph below taken from Stephan’s video lecture.

Leptin fat cycle

This is a sophisticated circular system that ensures our body fat remaining relatively constant over time. This system works perfectly well unless it is disrupted by the following factors: excessive leptin, inflammation and lipid metabolites. Let’s explain these factors one by one:

  1. Excessive leptin: Leptin level is proportional to body fat mass. So if you have too much body fat, it will produce excessive leptin, which disrupts the leptin-fat cycle. The consequence is: your brain doesn’t tell you to stop eating and you will keep on take in more calories and storing more fat. More fat->more leptin->more fat. Your body becomes a fat production line without a stop button! Pretty scary, isn’t it?
  2. Inflammation: We all have millions of gut bacteria in our digestive system. They help us with the digestion and nutrient absorption and live in harmony with us. But if we keep on eating unhealthy diet, our gut cells become “leaky” and these harmless bacteria can now enter our circular system and cause inflammation. Inflammation will disrupt the leptin-fat cycle and we will lose control of our fatness. What makes it worse, excessive fat mass is also inflammatory. This viscous cycle goes on and make us obese.
  3. Lipid metabolites: The fat we eat is normally metabolized and used as energy source for the cells. But when there is too much fat, the lipid metabolites accumulates in the cells and make the cells less sensitive to leptin. Thus the leptin-fat cycle is disrupted and we will enter the viscous cycle that leads to obesity.

The following diagram (also taken from Stephan’s lecture) summarizes the causes for leptin resistance:

leptin causes

Take away message from this lecture is: overeating, obesity, unhealthy food (especially refine, processed food) and inactivity can lead to excessive leptin, inflammation and lipid metabolites, which in-turn causes leptin resistance.

Leptin and fat are very much like the Chinese yin and yang. They are two opposite forces give rise to each other. When yin gets stronger, yang will suppress it and vice versa. They are in constant movement but at the same time maintains harmony and balance. Thus the balance is maintained all the time unless one gets too strong and break the cycle.

The best way to prevent obesity is maintain the balance between leptin and fat and do not enter the viscous cycle. Eating healthy food and regular physical activity can reduce inflammation and regulate level of leptin and lipid metabolites.

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