weight & body fat
nutrition
PYY

How Does This Tiny Protein Stop You From Eating Too Much? (PYY)

Written by Jasmine Foster, BSc, BEd on June 29th, 2020
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PYY is a brain signalling protein that reduces appetite and food intake. Which variants are associated with weight gain and obesity? Learn more here.

What is PYY?

Neuropeptides are small proteins used to transmit signals in the brain, and neuropeptide Y (NPY) is one of the most abundant of these, along with peptide YY (PYY) and pancreatic polypeptide (PP) [R].

PYY reduces appetite and discourages eating. This peptide may also increase energy usage; mice with overexpressed PYY run higher body temperatures than normal, for example [R].

How Does PYY Control Appetite & Weight Gain?

PYY is what’s called an anorexigenic or anorectic compound, meaning that it reduces appetite and food intake [R, R].

One study found that mice with increased PYY were protected against obesity, even when they were fed diets that should have made them gain weight [R].

This peptide has such a strong effect on body weight that it has been considered as a potential treatment for obesity. In multiple rat and mouse studies, injecting PYY into the brain led to dramatic weight reductions in appetite and subsequent weight loss; however, researchers have struggled to reproduce this result in humans or to find substances that dramatically increase PYY in humans [R].

PYY is a neuropeptide that reduces appetite and food intake. According to animal research, it may also increase energy usage. All of these effects promote weight loss.

PYY Variants & Weight

Three PYY variants have been associated with weight gain in humans: rs162430, rs162431, and rs2070592 [R, R].

At rs162430, the ‘A’ allele was more common in obese children than in children of healthy weight. This allele was also associated with severe obesity in indigenous Pima men [R].

At rs162431, the ‘T’ allele is associated with increased PYY and reduced body weight in a group of people of mixed ancestry (a sample that suggests that this allele has a similar effect regardless of ethnicity) [R].

Finally, at rs2070592, the ‘C’ allele is associated with reduced PYY gene expression and increased total cholesterol. This association was especially strong when combined with the common ‘G’ allele at rs162431 [R].

Your PYY Results for Appetite

SNP Table

variant genotype frequency risk allele
rs162430
rs162431
rs2070592

 

SNP Summary and Table

PYY rs162430

  • ‘G’ = Not associated with obesity
  • ‘A’ = Associated with obesity in children and in indigenous Pima men
  • About 55% of all people worldwide have at least one copy of the ‘A’ allele.
  • The ‘A’ allele is much more common in people of East Asian descent (89%) and much less common in people of European descent (18%).

PYY rs162431

  • ‘G’ = Associated with relatively decreased PYY and increased body weight
  • ‘T’ = Associated with relatively increased PYY and reduced body weight
  • The ‘T’ allele is relatively rare, and the population frequencies of various genotypes at this SNP are poorly studied.

PYY rs2070592

  • ‘T’ = Associated with relatively increased PYY and reduced total cholesterol
  • ‘C’ = Associated with relatively reduced PYY and increased total cholesterol
  • About 67% of all people have at least one copy of the ‘C’ allele.
  • The ‘C’ allele is much more common in people of East Asian descent (89%) and much less common in people of European (55%) and South Asian (47%) descent.

 

Recommendations

Lifestyle

A Good Night’s Sleep

One study found that reduced sleep duration, even for a single night, was found to reduce PYY expression in young men. The authors of this study concluded that getting a good night’s sleep is essential for normal regulation of appetite [R].

Short sleep duration has been associated with weight gain in many studies. A meta-analysis of 30 studies and over 630,000 people associated short sleep duration with a 55% higher incidence of obesity in adults and 89% in children [R, R, R].

Poor sleep can increase hunger and cravings and disrupt hunger hormones like ghrelin and leptin [R, R].

Stress Management Strategies

At least one study has found that psychological stress prevents PYY secretion in women [R].

Stress is known to cause weight gain. Stress increases cortisol and dynorphin, both of which cause weight gain [R, R, R].

It also increases glutamate, which increases appetite, while decreases NGF and BDNF, both of which are appetite suppressants [R].

Additionally, it makes the brain resistant to serotonin, a neurotransmitter that also suppresses appetite. Stress also causes resistance to dopamine, which may cause us to eat more as we’ll need to eat more food for the same rewarding effects [R, R, R].

Reduced sleep duration and increased stress can both reduce PYY secretion, so it’s important to get a good night’s rest and to practice stress management.

Diet

High Protein Diet

Eating protein has been found to increase production of PYY in animals, possibly leading to reduced food intake and weight loss [R].

Some research suggests that getting more calories from protein (as opposed to either carbohydrates or fat) may support weight loss, metabolism, and satiety. High-protein diets appeared to increase fat burning and weight loss and reduce appetite in a handful of human studies [R, R, R].

Reduce Carbs

A diet high in carbohydrates has been found to result in less PYY circulating in the blood compared to a diet high in other macronutrients [R].

Insulin is one of the big four fattening hormones. High glycemic index carbs will cause insulin spikes and insulin resistance, ultimately increasing your risk of obesity. However, they also increase satiation in the short term [R].

In a clinical trial on 119 overweight people, a low-carbohydrate ketogenic diet was as effective as a low-fat diet for weight loss but had the advantages that it reduced appetite and negative affect. A meta-analysis of 13 studies and over 1,500 people concluded that low-carbohydrate ketogenic diets are more effective than low-fat diets for losing weight [R, R].

Protein-rich foods increase production of PYY, while carbohydrate-rich foods generally decrease it. A diet higher in protein and lower in carbs may promote PYY.

Resistant Starch (Increase Fiber)

Some evidence suggests that resistant starch may help promote weight loss in certain circumstances. Some researchers believe that this effect relies on the fermentation of soluble fiber and resistant starch in the gut: beneficial bacteria digest these complex carbs, producing butyrate, which in turn signals the body to produce PYY [R, R].

In obesity-prone rats, dietary resistant starch and regular exercise prevented weight gain, apparently by reducing food intake [R].

Vegetables are rich in soluble fiber, which has been shown to cause weight loss in some studies. Fiber gets broken down by bacteria in the digestive tract to produce butyrate, which has weight loss effects in animals [R, R, R, R].

Resistant starch may stimulate fat burning by:

  • Reducing fat accumulation and increasing fat oxidation after meals [R].
  • Forcing the body to burn fat by lowering blood glucose [R].
  • Decreasing fat production while increasing the production of phospholipids [R].

When resistant starch is fermented by beneficial gut bacteria, the reaction produces butyrate. This fatty acid appears to signal the body to produce PYY.

Supplements

Butyrate

Butyrate, the fatty acid produced when good gut bacteria ferment resistant starch, signals the body to produce PYY [R].

In a trial of 118 overweight people, fiber supplements (which the gut flora convert to butyrate) also led to reduced body weight and BMI. Animal studies have also generally found butyrate to be protective against weight gain [R, R].

Meanwhile, in a trial of 12 men, short-chain fatty acids (including butyrate) delivered directly into the colon increased the amount of fat being burned and energy being spent [R].

Short-chain fatty acids may prevent weight gain and obesity through several mechanisms, including [R]:

  • Revving up fat burning (enhancing triglyceride breakdown and fatty acid oxidation)
  • Transforming fat cells into brown fats, which are more easily burned for energy [R]
  • Promoting the generation of new mitochondria
  • Inhibiting chronic inflammation

Butyrate is available as a supplement, but the best way to deliver butyrate in the colon is by feeding resistant starches to the gut flora and ensuring that the gut flora remains healthy. These bacteria are well-established contributors to human metabolism and weight [R].

Butyrate, which stimulates PYY production, is also available as a supplement.

Berberine

Rats fed a high-fat diet produce less PYY and gain than those fed a healthy diet; however, researchers found that giving these same rats berberine restored PYY to normal levels [R].

Berberine is an alkaloid with potent metabolic effects. People use berberine as a supplement to support weight control and glucose metabolism.

Berberine supplementation reduced BMI and enhanced leptin sensitivity in 37 patients with metabolic syndrome. In another study, it caused an average weight loss of 5 lbs (2.3 kg) and lowered blood lipids [R, R].

According to a 2020 review of human and animal studies, berberine might contribute to weight loss by improving gut microbiota and glucose and fat metabolism [R].

Berberine normalized PYY production and promoted weight loss in animal and human studies.

EGCG

EGCG, the major polyphenol in green tea, increased PYY production in a cell study; its effect in animals or humans is unclear [R, R].

EGCG caused between 0.2 and 3.5 kg of weight loss in limited human studies. Green tea, meanwhile, is hypothesized to make us burn more calories, even at rest. In most studies, this amounts to a modest 3-4% increase in energy, though some studies have shown an increase as high as 8%. For a 2,000 calorie diet, 3-4% amounts to an additional 60-80 calories per day [R, R, R, R, R, R].

In one study of 60 obese individuals, the group taking green tea extract lost 7.3lbs and burned 183 more calories per day (on average) after 3 months [R, R].

According to a review of 11 studies, green tea extract or EGCG can slightly improve weight loss and maintenance. However, a Cochrane database review of 14 studies regarded the change in weight as nonsignificant in most studies, so the evidence is inconclusive [R, R].

The majority of weight loss trials used special extracts with higher concentrations of active ingredients (catechins and caffeine), compared with regular tea. Hence, it may be necessary to take an EGCG-rich green tea extract for beneficial effects [R].

EGCG from green tea increased PYY production in cells and has been linked to weight loss in human studies.

Forskolin

A tissue study found that exposure to forskolin in the intestine could cause the release of PYY [R].

In small human studies, forskolin decreased body fat in both men and women [R, R].

In one clinical trial on 30 overweight and obese people, Coleus forskohlii (together with a low-calorie diet) reduced weight gain, insulin resistance, and blood cholesterol (by increasing HDL). This suggests that the intervention reduced the risk of metabolic syndrome [R].

Another trial on 30 obese men found a decrease in body fat, increased testosterone levels, and improved bone structure after forskolin administration. However, a trial on 32 men found that the fat-burning effect of forskolin was lower in middle-aged compared to young men [R, R].

In another trial on 23 overweight women, C. forskohlii extract did not cause weight loss directly, but prevented weight gain and did not have the side effects of other weight-loss supplements  [R].

Forskolin, a promising compound for weight loss, caused PYY to be released in an intestinal tissue study.

Probiotics

As we’ve discussed, the fermentation of soluble fiber and resistant starch by beneficial gut bacteria seems to cause an increase in PYY. Gut fermentation has also been linked to increased PYY more broadly; certain probiotic bacterial species may  [R, R].

  1. gasseri significantly decreased BMI, abdominal visceral fat, waist and hip circumferences, and body fat mass in 210 healthy Japanese adults, with an 8.5% decline in abdominal fat area over twelve weeks. However, the authors warned that constant consumption of this probiotic may be required to maintain this effect [R].

In a clinical trial of 125 obese adults, L. rhamnosus induced weight loss, reduced fat mass, and reduced circulating leptin [R].

Additionally, L. rhamnosus CGMCC1.3724 improved liver parameters in a small trial of 20 obese children with liver dysfunction noncompliant with lifestyle interventions [R].

Humans with more B. animalis have lower BMI, while those with less of this bacteria have higher BMI [R, R].

Daily ingestion of milk containing B. animalis ssp. lactis significantly reduced the BMI, total cholesterol, low-density lipoprotein, and inflammatory markers in a clinical trial on 51 people with metabolic syndrome [R].

Gut fermentation may trigger an increase in PYY production. Some probiotic supplements have also been found to promote weight loss in human trials.

Hops Extract

In a mouse study, a bitter-tasting compound extracted from hops increased PYY secretion by about ten times [R].

In a trial on 200 healthy overweight people, hops extract reduced body fat, especially in the belly [R].

Both hops extract and its components xanthohumol and iso-α acids reduced body weight in multiple studies in overweight mice and rats [R, R, R, R, R].

Xanthohumol also reduced the development, growth, and fat accumulation of fat cells while increasing their death rate [R, R].

The combination of hops isohumulones and acacia proanthocyanidins improved several symptoms of metabolic syndrome. Together with diet changes and physical exercise, it decreased blood levels of triglycerides and cholesterol (total, LDL, APOB) in a trial on 23 people. The combination also reduced insulin levels while increasing insulin sensitivity in another trial on 91 people [R, R].

Bitter-tasting compounds from hops increased PYY secretion in mice and promoted body fat loss in a human study.

Author photo
Jasmine Foster
BSc, BEd

Jasmine received her BS from McGill University and her BEd from Vancouver Island University.

Jasmine loves helping people understand their brains and bodies, a passion that grew out of her dual background in biology and education. From the chem lab to the classroom, everyone has the right to learn and make informed decisions about their health.

Disclaimer

The information on this website has not been evaluated by the Food & Drug Administration or any other official medical body. This information is presented for educational purposes only, and may not be used to diagnose or treat any illness or disease.

Also keep in mind that the “Risk Score” presented in this post is based only on a select number of SNPs, and therefore only represents a small portion of your total risk as an individual. Furthermore, these analyses are based primarily on associational studies, which do not necessarily imply causation. Finally, many other (non-genetic) factors can also play a significant role in the development of a disease or health condition — therefore, carrying any of the risk-associated genotypes discussed in this post does not necessarily mean you are at increased risk of developing a major health condition.

Always consult your doctor before acting on any information or recommendations discussed in this post — especially if you are pregnant, nursing, taking medication, or have been officially diagnosed with a medical condition.

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