# RKS: HORMONES & OBESITY - The Little Known Link

 

# RKS: HORMONES & OBESITY 

THE LITTLE KNOWN LINK

1st October 2023

GHRELIN - THE SAGA & ENIGMA

EXPLORING OBESITY HORMONES MODULATING POSSIBILITIES

Dear Reader,

Ghrelin stimulates the brain, which leads to an increase in appetite, and it slows metabolism and decreases the body's ability to burn fat. Ghrelin also favors the amassing of fatty tissue in the abdominal area. Hence, Ghrelin is a do-all hormone as far as obesity is concerned.

If Ghrelin is this the key hormone playing a role in obesity it could make fascinating reading about the same since globesity is the current most prevalent scourge of mankind.

ALL ABOUT GHRELIN

Ghrelin is produced by the stomach and is famously known as the ‘hunger hormone’. It is a multifaceted hormone since, besides stimulating food intake, Ghrelin participates in many other functions which directly or indirectly contribute to obesity.

Fig: Ghrelin actions.

It is well-documented that Ghrelin is an orexigenic hormone – i.e. it facilitates increasing energy intake and its storage as well. Ghrelin promotes build up of adipose tissue (adipogenesis) and fats (lipogenesis) and even prevents breakdown of lipids (lipolysis is inhibited).

GHRELIN PARTNERS GROWTH HORMONE

All those who are overweight or obese consider Ghrelin as a villain since this hormone makes one eat! When someone overeats it is hyperphagia and Ghrelin is responsible for the same.

Human Growth Hormone (HGH), as the name suggests, makes the body grow by thickening and elongating bone as well as by growing muscles. It is secreted by the pituitary gland in the brain. 

There are Growth hormone secretagogue receptors (GHSR) in brain and Ghrelin stimulates these. As a result, the HGH levels in the body rises and this hormone then pings the pancreas to release insulin. As a result of more insulin concentration in blood there is intense hunger experienced and resultant immediate urge to uninhibitedly consume food.

'GO’ HORMONE vs ‘STOP’ HORMONE

Because Ghrelin makes one splurge on food, it is also called as ‘GO’ hormone. The opposing hormone to Ghrelin is Leptin which is known as the ‘STOP’ appetite hormone. Leptin is a hormone produced in the fat cells. It plays a role in regulating body weight by signalling the brain to reduce appetite and burn more calories. 

Leptin, the ‘STOP’ hormone suppresses the appetite centre which is present in the hypothalamus region of the brain. It is the same very appetite centre that the insulin stimulates to make one feel hungry!

Thus, the ‘GO’ hormone Ghrelin makes one consume food and energy, whilst the ‘STOP’ hormone Leptin halts intake of unnecessary calories. This makes the hypothalamus a master regulator of satiety. 

ADIPONECTIN & CORTISOL – ADDED OBESITY INFLUENCERS

ADIPONECTIN

Adiponectin is a hormone manufactured by the adipose tissue. It opposes Leptin since it is more released when one is hungry. Adiponectin contributes to the release of HGH. As a result, as already elaborated, there is a rise in insulin production followed by the stimulus to appetite centre to initiate eating.

Adiponectin promotes burning of fats selectively. This hormone strangely promoting fat storage in subcutaneous fat pads instead of visceral fat pads, liver or skeletal muscle. Thus, the obesity may not be reduced but the associated risk of heart disease and diabetes decline.

Fig: List of hormones influencing obesity.

If the body has excess energy stored as fat, Leptin signals the hypothalamus to reduce appetite and burn excess body fat for fuel.

CORTISOL

Cortisol is a steroid hormone that is produced by the two adrenal glands, which sit on top of each kidney. When one is under extreme duress increased Cortisol is released and it is this hormone that is important for fight-or-flight response which manifests as increased heart rate (tachycardia), anxiety, increased perspiration and tremors associated during any stressful situation.

Recent studies have demonstrated that Cortisol levels are increased in people with obesity compared to those having normal-weight. High levels of Cortisol increase appetite with a preference for “comfort food” and cause white adipose tissue to redistribute to the abdominal region, which ultimately lead to abdominal obesity. Chronically high Cortisol even increase the ability of fat cells (adipocytes in adipose tissue) to store fat.

MODULATING OBESITY HORMONES

Summarizing, it makes logical sense to decrease the levels of Ghrelin and Cortisol and increase that of Leptin if obesity is to be tackled physiologically.

 

CORTISOL

Globally available medicines to reduce Cortisol levels are:

1. CONTROL CORTISOL PRODUCTION: Ketoconazole / Levoketoconazole, osilodrostat, mitotane, metyrapone 
2. CORTISOL BLOCKERS: Mifepristone, pasireotide

All these above drugs are approved only for Cushing’s disease, which is caused by consuming excess of corticosteroids, and not for otherwise normal individuals battling obesity.

Fig: Supplements and diet to reduce Cortisol levels.

Adrenocorticotrophic Hormone (ACTH) is produced by pituitary gland and this hormone stimulates the adrenal glands to manufacture cortisol.

LEPTIN

The body burns calories consumed during the day for the first six to eight hours after eating dinner. The most efficient fat-burning period is between the 8th and 12th hour after dinner. Having a snack before bedtime or a late evening meal stimulates Leptin release, which informs the brain that no more energy is necessary, so no fat will be burnt throughout the night.

Eating at least three hours before bedtime allows leptin to burn fat while keeping other hormones in check during the night.

Fig: Supplements and diet to increase Leptin levels.

Those who do not get a good night’s rest have a 15% lower Leptin level than those who sleep sufficiently; Leptin levels typically rise during the sleep cycle.

GHRELIN

 If Ghrelin stimulates hunger, a Ghrelin inhibitor (antagonist) will be effective in helping people lose weight? Several pharmaceutical companies have or are conducting research on such a compound. The Scripps Research Institute in California in 2006 successfully developed an anti-obesity Ghrelin vaccine that significantly slowed weight gain and reduced body fat in animals. It is possible that in the future there will be a Ghrelin blocking medication. But, since Ghrelin also makes eating food more pleasurable, a drug blocking the brain’s pleasure centre might create side effects related to mood regulation.

The research on Ghrelin blockers is no slam dunk. A promising medication called rimonabant, which works by interfering with one of the brain’s cannabinoid receptors, was successfully demonstrated to cause weight loss. However, rimonabant also affected the pleasure centre in the brain and side effects included the potential for severe depression, sometimes leading to suicide. This drug was thus not approved for use to reduce Ghrelin in obese individuals due to these side effects.

Fig: Supplements and diet to decrease Ghrelin levels.

Consuming eggs for breakfast influences plasma Ghrelin levels, whilst reducing energy intake during the next 24 hours in adult men.

CONCLUSIONS

If one could create our bodies for one day, perhaps one would simplify the actions of Ghrelin and Leptin and overcome the appetite stimulating effects of the “hunger hormone.” Beyond this wish, the reality is that the human body has a complex system of hormones that interact in countless ways. Therefore, it is unlikely that a simple one-to-one relationship can be found between these hormones and weight. That hormones like Ghrelin and Leptin are likely part of a chain of physiological processes is too bad. However, one can seek to countermine a villain, i.e. Ghrelin, when considering the challenges of obesity. More research is needed before firm conclusions can be drawn about the effects of Ghrelin.

Obesity - all hopes are never lost. Explore safer options.

Only drugs cannot be the bottom line.

&

(life-long) Dieting is not everyone's cup of tea.

The Mantra for tackling adverse impacts of obesity-influencing hormones should be: 

- Consider consuming suitable supplements.

- Relish eggs for breakfast.

- Eat 3 hours before bedtime.

- Sleep for 8 hours per day.

DR R K SANGHAVI

Prophesied Enabler

Experience & Expertise: Clinician & Healthcare Industry Adviser

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