Excess weight is one of the negative aspects that have been characterizing western societies since the end of the cold war. Several trials have been made to limit this phenomenon, and a variety of protocols have been suggested, from increased physical exercise to semi-starvation, from surgically limiting the size of one’s stomach to encouraging the intake of non-caloric beverages, from liposuction to hypnosis, all with limited success, if any.

Now that the market offers drugs that seem to be able helping one losing weight for real, a recurrent question concerns the expected effects of weight loss on the skin. I will try and give an answer, albeit tentative. The real answer will be given when a large enough cohort of people having lost weight thanks to these drugs will be available for clinical scrutiny.

So, to tackle the question, let’s make a recap of energy metabolism, first, and of the elastic properties of the skin, afterwards.

Energy Metabolism (Kindergarten Level)

The fuel for every animal activity, humans included, is a molecule called ATP (adenosine tri-phosphate). ATP is unstable and it cannot be stored. When needed it is extemporaneously prepared. 

A biochemical process called glycolysis or Embden-Meyerhof pathway transforms glucose into pyruvate while producing two molecules of ATP. Pyruvate is then metabolized to acetyl CoA that binds to endogenous oxaloacetate. 

The Krebs Cycle, also called the citric acid cycle, metabolizes the acetyl CoA-oxaloacetate complex into a variety of molecules and back to oxaloacetate while producing one molecule of ATP per original pyruvate molecule. The newly formed oxaloacetate will bind to the next acetyl CoA molecule and the cycle resumes.

Since our meals are not solely composed of glucose (luckily so!) one can ask where we find the glucose necessary to feed all the energetic needs for our muscular and intellectual activities. It turns out that we can generate energy while enjoying French gourmet dishes because a complex biochemical process called gluconeogenesis generates glucose from lactic acid, proteins and fat, and this glucose will serve as a substrate for glycolysis.

When glucose is in excess, it can be metabolized and stored in the form of triglycerides in the cells of the adipose tissue, or it can be polymerized to form glycogen and stored in other cells. 

When the individual is under stress and in the immediate need of energy, epinephrine signals muscle cells to digest glycogen and ATP is formed that will help one surviving when, for instance, one is in a fight or flight situation.

In the case of starvation, glucose can be slowly generated via gluconeogenesis using the glycerol from the triglycerides in the fat tissue or can be quickly released by the degradation of glycogen. The degradation of glycogen in the liver is controlled by a hormone called glucagon, that signals when the level of glucose in the blood is low. 

A signaling mechanism is also associated to a hormone produced in intestinal cells. This hormone is GLP-1 (Glucagon-like Protein 1). When GLP-1 binds to its receptor, it inhibits the release of Glucagon, thus hindering the degradation of glycogen. 

When GLP-1 is in action, the only remaining way to generate free glucose is the neoglucogenesis using stored fat. 

GLP-1 also signals to the brain the feeling of satiety, so that we stop eating. 

This means that when GLP-1 is at work, one will eat less food and degrade more fat.

The drugs presently on the market to help people lose weight are molecules that boost the binding of GLP-1 to its receptor (such molecules are called GLP-1 receptor agonists). 

Their final effect is that the fat stored in the adipocytes will be digested and the adipose tissue will shrink, with weight loss as one of the consequences.

And What about the Skin?

Esthetic surgeons know that skin is extensible. One of the ways to surgically treat alopecia was to make an incision in the scalp at the “frontier” between the hairy and the bald parts. A balloon could then be introduced under the scalp. The balloon could then be inflated, thus achieving an extension of the scalp over the next several months. After resection of the excess skin, the two remaining parts of the scalp could be sewn together so that, at the end of the process, the area of the head effectively covered by hair was increased.

Because skin is extensible, one can surmise that upon losing weight because of the shrinking of the adipose tissue, the skin covering the overweight part of the body will be overextended. One of my friends who is a humorless engineer told me that if we assume the human body to be a sphere, losing one kg of adipose tissue will provoke a decrease of 0.1 cm of the body radius and will result in 0.6 cm excess skin. This number seems to be negligibly small. And yet in anatomical regions where the adipose tissue is quite thick, of the order of several centimeters, and in the case of severe weight loss, the resulting “excess skin” might be unwelcome and might require surgical body contouring. This comprises face and neck surgeries, chest surgeries, abdominal surgeries and brachioplasty. But every body is different and responds differently to weight changes. Not all individuals will experience the same issues related to loose skin after losing weight.

As far as the face is concerned, we know that one of the signs of aging is the “triple chin” that is the result of the mobilization of the fat from the cheeks to the jaw. In this case, losing fat in the face would be welcome. For sure, we do not know yet much about the stereophysics of weight loss, and predictions are difficult, particularly when it comes to the structure of the face, that is far from being spherical!

Paolo Giacomoni, PhD of Insight Analysis Consulting acts as an independent consultant to the skin care industry. He served as executive director of Research at Estée Lauder and was head of the department of biology with L’Oréal. He has built a record of achievements through research on DNA damage and metabolic impairment induced by UV radiation as well as on the positive effects of vitamins and antioxidants. He has authored more than 100 peer-reviewed publications and has more than 20 patents. He is presently head of R&D with L.RAPHAEL—The science of beauty—Geneva, Switzerland. His email is: paologiac@gmail.com.