What Many Think Weight Loss Should Look Like

The NCDs hypertension, CVD and T2D are multifactorial diseases that develop over a long time. Interestingly, they all seem to have one metabolic origin in common: Obesity and systemic chronic inflammation.

Drugs are available to treat and manage T2D and CVD successfully; hypertension due to obesity is often drug resistant though. The best treatment for all three would be a healthy lifestyle and weight loss. Losing weight will reduce the chronic systemic inflammation and slows the disease progression. After weight loss is achieved blood pressure will often return to normal, blood lipids will improve and insulin resistance can improve to the point of reversal.

Before we even look at the scientific data for weight loss and metabolic improvement, you should wrap your head around what weight loss even means. Thanks to Instagram browsing, most of us would probably conjure up a picture like the one to the left. Today, weight loss is often defined as reaching a toned, thin body for women and a body with visible, larger muscles for men.

Most people will not reach this ideal because their genes and life circumstances will not allow them to. Others will reach this ideal briefly, but will return over the next years back to their old weight. A study following participants from the TV show The Biggest Loser demonstrated this very clearly. All but one study participant regained at least some of the lost weight within 6 years.

The point I’m making here is that as health professionals we are not defining weight loss that way. Make sure that the weight loss you are talking about in the context of metabolic improvement is:

• Slow weight loss. Metabolic improvement can be seen with a weight loss of only 5 % of the body weight.
• Weight loss, no matter how much, needs to be maintained.
• The focus should be on an increasingly healthy lifestyle not on looks.

As usual, recall what you already know. If not review:

Maybe you also have a look at the NUTR250 Nutrition and Metabolism chapter about energy balance. Reviewing will help you gain a better understanding and will solidify the science.

Eat Less, Exercise More? It is Not That Simple

Overweight and obesity are contributed to an imbalance between energy intake and energy expenditure. This is a scientific fact. The paradigm Eat less, exercise more was the standard recommendation for maintaining a healthy body weight for a long time.

The scientific fact of a positive energy imbalance is often mixed up though with the much more complicated question why this positive energy imbalance happens in so many people today. While some are still pushing the old, simplistic recommendation, we know today that the regulation of energy balance and with that the maintenance of body weight is much more complex than this simple  recommendation.

Before we look at the consequences of obesity in more detail you should understand the principles of food intake regulation.

There are the two major physiological pathways regulating food intake.

One is the homeostatic pathway that regulates the homeostasis between energy intake and expenditure. This pathway increases the motivation to eat when energy stores are depleted or increases satiety when sufficient amounts of food were eaten.

The command center of the homeostatic pathway is the brain and there are three major inputs.

The first input is the secretion of digestive hormones. After food is digested and the stomach is empty the stomach starts secreting ghrelin. Once we eat and the stomach fills pressure receptor read the degree of expansion. Ghrelin secretion subsides. The hypothalamus reads the amount of ghrelin circulating the blood stream. High ghrelin stimulates feelings of hunger while declining ghrelin increases the feeling of satiation.

While food is digested other digestive hormones are secreted by the stomach and small intestine. These hormones coordinate the digestion but also prepare the metabolism for the incoming nutrients. The third function is feedback to the brain to suppress appetite depending on macro-nutrient composition and food amount. This is the reason why we usually do not have a drive to eat right after a meal.

The second input is the signaling from existing energy stores. Leptin is one of the hormones involved here. Again, the hypothalamus in the brain monitors leptin blood concentrations. A decrease of leptin secretion with shrinking adipose tissue increases the drive to eat. Increasing leptin secretion with growing adipose tissue tends to reduce appetite.

Interestingly, the drive to eat during an energy shortage is much more potent than the down regulation when energy becomes abundant again. As a result gaining weight is much easier than losing weight.

The third input is the energy expenditure. Even when we are at rest our metabolism will require energy. Increasing energy expenditure for example due to exercise is also read. Newer research also shows that the drive to physical activity and exercise is not completely determined by our behavior. The hypothalamus can trigger spontaneous physical activity (SPA) which increases energy expenditure. SPA is increased during a positive energy balance (leptin ↑) and reduced during a negative energy balance (ghrelin ↑).

Eating does not just provide energy and nutrients but is also a pleasurable experience. This is where the second pathway, the reward-based regulation or hedonic pathway, comes in. The inputs for the hedonic pathway vary and are complex. These cues mostly stimulate the pleasure center of our brain.

During times of abundant food supply the hedonic pathway will override the homeostatic pathway by increasing the desire to eat palatable foods. Today’s food environment supports this physiological overeating by providing ubiquitous and abundant amounts of very tasty food.

Cues stimulating the hedonic pathway can be cognitive. Sensory cues such as seeing, smelling and tasting delicious food increases food consumption. Habitual eating behavior and our social environment also alter food consumption. Some individuals have excessively restricted eating behaviors while others eat uninhibited. Emotions ranging from being bored to happy to sad to stressed can also influence how much we eat. How much those psychological factors impact eating decisions varies widely between individuals.

In the past long gone most people were exposed to food only during meal times when they actively sought out food. Today our environment impacts our eating behavior. External cues such as the constant presence of food or food advertising trigger more and frequent eating. Food availability, geographic and economic, determines what food we eat. Many social interactions are connected to food. Nutritional and non-nutritional factors such as food composition, meal size, plate or serving sizes alter our eating behavior. For example people eat more when served a larger portion.

In conclusion: The hedonic regulation tend to override the homeostatic energy regulation in today’s obesogenic food environment. As a consequence overeating is common. In addition, once weight is gained metabolic changes to the homeostatic pathway makes it easier to gain weight and harder to lose it.

This said, we all react differently to the food environment. Eating behavior develops during childhood and early adulthood based on our food and eating experience which is determined by our social environment, cultural experience and education.

In part this explains why the old eat less, exercise more weight loss recommendation fails.

Substantial Weight Loss Is Possible, But Maintenance of the Lower Weight Is Elusive For Most

Losing 5% weight to improve or restore metabolic health? Sounds easy enough? Initial weight loss might be reasonably easy to achieve but the maintenance of the lower weight is extremely difficult.

The graph below shows the development of average weight in seven long-term weight-loss studies. During the 6 months of active weight loss the participants showed a weight loss between 5 and 15 % of the starting weight. This weight loss is enough to improve metabolic health. But, with exception of one study weight was gained back during the next 3 to 5 years.

During the initial weight loss phase the degree of adherence to the diet (or exercise program) is the key weight loss success. When it comes to the type of weight loss diet, high protein/low-carbohydrate diets or the keto diet trigger more initial weight loss but once weight loss slows down many other weight loss strategies catch up. People lose weight on all diets as long as the energy balance is negative.

The important part is that very consistently—no matter what diet—the adherence to the diet starts waning around the 6 to 9 months mark. Most weight loss journeys no matter the diet show the following phases:

1. Rapid initial weight loss
2. Slowing weight loss until a plateau is reached around 6 – 9 months
3. Slow regain of the weight over the next years

Individuals on low-carb diets tend to start eating more carbohydrates. Individuals on low fat, high carbohydrate diets tend to eat more fat and less carbohydrates. Habitual eating habits that caused the weight gain in the first place sneak back into the dietary pattern. The faster the adherence wanes the faster the weight is regained. In average, people regain weight at a rate of 1 – 2 kg per year. This regain is faster right after the weight loss and then slows down somewhat.

Scientists wondered what exactly happens at this tipping point of 6 – 9 months. A NIH working group reviewed the evidence of weight regain in 2015 and came to the conclusion that “One explanation for the declining adherence is that the perceived costs of adherence gradually exceed the perceived benefits. Initially, the positive consequences of weight loss (e.g., sense of accomplishment; better fit of clothes) outweigh the cognitive and physical effort needed to lose weight. Later, when the goal is to maintain lost weight, the positive feedback is less compared to the effort required to keep adhering to the same regimen. Thus, the benefits no longer seem to justify the costs.”

While we cannot predict who will be successful and who will regain weight, studies identified two traits that seem to make continued maintenance of the lower weight more likely:

• People who show a faster and larger weight loss tend to do better at maintaining the lower weight.
• Highly motivated people are more successful maintaining the weight loss.

Losing weight looks different for each individual person. However, if individuals want to succeed then it is crucial to acknowledge that it won’t be a steep steady decline in weight all the time. There will be periods of slow weight loss while for other periods there might be a weight plateau. Vacations, holiday seasons, birthday parties, or phases of stress might even trigger some regain of weight. The patient record below shows an example of successful weight loss and maintenance. This is what real long-term weight loss looks like.

Note the rapid initial weight loss, slowing of weight loss until reaching a plateau. There is also weight regain until new weight loss is triggered.

Obesity Alters The Regulation of Body Weight Profoundly

It was always clear that weight loss maintenance is much more difficult than weight loss. Behavioral explanation seemed to explain this. Most people feel that they have “finished weight loss” once they reach a desired weight. Weight loss behaviors such as regular exercise, self-monitoring, contingency plans feel tedious and cease. In addition, weight loss comes with a feeling of success such as smaller clothing sizes, completing daily tasks easier, better health, and lots of compliments. During the weight loss phase calendars are adapted and families accommodate the peron on a weight loss journey in support. Weight maintenance is going back to normal. No successes, no compliments for maintaining the lower weight.

Over the last decades scientists also started to understand that weight loss alters metabolic regulation of eating profoundly which in turn impacts eating behavior. Many motivated people are still gaining weight because nature is working against them.

In its simplest form weight regulation is a feedback loop between the brain and the body periphery. The periphery signals the status of energy stores and energy balance. When energy stores decrease the brain increases the efficiency of energy use, triggers a preference for palatable foods, and decreases satiety. If more energy is spent than consumed the feedback loop triggers hunger and eating more. Interestingly, the feedback loop is also buffering occasional over- and undereating. If we overeat on some days our energy metabolism becomes less efficient and burns more calories. If we undereat we become less energy efficient and burn more calories. This is called the settling point.

What we expect after weight loss is that the body settles into the new, lower weight. That doesn’t happen though. The regulation of the energy intake and expenditure is uncoupled.In the new metabolism the goal of the energy metabolism is to get back to the higher weight.

A study following participants of the Biggest Loser demonstrates this. The scientists looked at the RMR of participants after 6 years. To their surprise the researchers found that the RMR was in average 500 kcal/d lower than expected. There was a large individual variation between study subjects though ranging from a 292 – 706 kcal/d deficit.

At the same time metabolic changes increased the driver to eat after weight loss.

The key to energy homeostasis are the hormones leptin and ghrelin.

As you already know Leptin is secreted by the adipose tissue and the amount of leptin secreted is proportional to the size of the adipose tissue. Leptin’s major function is to signal the status of the adipose tissue to other organs. Losing adipose tissue decreases leptin secretion. This signal is picked up by the brain and hunger increases.

Ghrelin is secreted by the stomach and does the opposite. A full stomach decreases ghrelin secretion and induces satiety. An empty stomach increases ghrelin secretion and the feeling of hunger.

Here is the problem. If someone becomes obese, the signaling of those hormones does not work as intended anymore. Gaining weight increases leptin blood levels initially. This should induce less hunger and increased satiety and restore the energy homeostasis.

However, if leptin blood levels are permanently high leptin resistance develops. The brain starts ignoring the high levels of leptin. If your brain stops listening, then it becomes harder for people to know when they are hungry and when they are full.

When weight is lost the adipose tissue produces less leptin. The brain interprets those lower leptin levels not as a good thing—keep in mind the brain lost track of the adipose tissue status a while ago—but as dangerous starvation. The brain starts energy conservation measures. We start craving more energy rich foods and eating will not induce satiety as easily. Energy use becomes super efficient and less energy is needed to maintain the existing adipose tissue stores. The RMR decreases.

The consequence  is a gap between the reduced energy needs and the increased food intake due to increased hunger. Weight is gained back.

Bariatric surgery is becoming common as a treatment option for obesity especially in severely obese individuals with chronic diseases.

During bariatric surgery part of the stomach is either tied off or removed creating a small stomach pocket or a bypass is created that directs food directly into the duodenum.

After bariatric surgery patients need to learn how to eat small portions of food and as a consequence they lose large amounts of weight rapidly. The weight loss can vary individually though as the graph below shows.

As you see not everybody has success. In somw patient weight is re-gained slowly after the initial weight drop. Stomach and intestines expand over time again allowing the patient to eat more and absorb more calories.

While bariatric surgery was invented to help severely obese patients to lose weight rapidly and hopefully maintain some of the weight loss, studies tracking some of those patients had a surprise in store. So far unexplained, bariatric surgery induces beneficial changes in hunger and satiety regulation as well as beneficial effects on glucose metabolism and insulin sensitivity.

Especially after the type of bariatric surgery that bypasses most of the stomach, ghrelin secretion decreases and PYY, another hunger hormone, increases. leaving bariatric surgery patients less hungry and allowing them to experience better satiety after a meal.

The incretin GLP-1, secreted by the pancreas and gut during digestion,  is involved in the blood glucose management. Increased GLP-1 results in more effective insulin secretion and better blood glucose regulation. This is thought to be the key to the immediate improvements of T2D after the surgery.

Bile acids emulsify fat but they also provide feedback about incoming fat to the metabolism and modify the gut microbiome. Increased secretion of bile acids is discussed to have positive metabolic effects.

Overall, bariatric surgery is an good option to jump start weight loss and metabolic improvements for metabolically unhealthy, obese people. Since bariatric surgery is a highly invasive surgery it will have the same dangers as any surgery. Obese individuals are especially vulnerable to complications during surgery and often have delayed woubd healing. The benefits need to outweigh the dangers.

Bariatric surgery will not magically fix all problems. The patient will still need to learn healthy eating, portion control and an active lifestyle.

Problem behaviors influencing appetite and unhealthy eating decisions are still kicking in after the novelty wears off. Behavioral intervention can help improve adherence and motivation.

Exercising And Ongoing Behavior Therapy Show Promise in Countering Biology

Bariatric surgery is able to counter biology to a certain degree. Positive changes in hunger and satiety will make it easier to lose and maintain weight. Considering the major downsides of the surgery this should not be an option for overweight and moderately obese, metabolically healthy individuals. The question is if there are other strategies to counter biology.

Regular exercise is a promising contender. So far we thought that weight loss is mostly mediated by healthier eating aided by an increased RMR when muscle mass increases. The physical exercise was thought to improve cardiovascular health and insulin resistance and aid dietary intervention.

Lately though evidence emerged that exercising also changes the energy regulation feedback loop. The research is still brand new but here are a few ideas that are proposed:

• People who exercise during weight loss have better adherence to dietary interventions. It is not clear why.
• Exercising affects appetite, food choices and overall intake.
• Exercise results in a more inefficient energy use—the muscle converts more energy into heat—increasing energy need.

Sounds amazing? These study results will be very frustrating for 50% of the American population. The additional beneficial effects of exercise are only seen in so-called exercise responders. Here is the frustrating part: Responders are more likely to be male.

Behavioral strategies also show promise. Research is looking into how the rewarding effect of palatable foods and cravings during weight loss can be countered. This includes modifying memories related to food, learning how to delay instant gratification, and improving impulse control.

Prevention of Obesity Is Easier Than Weight Loss

The weight loss and regain evidence makes it clear that once a person is obese it is very difficult to lose weight and maintain this weight loss. While we need to find better approaches to help obese people to improve their metabolic health the best approach would be to prevent obesity all-together.

Recently, an expert committee selected by the American Medical Association, in collaboration with the Department of Health and Human Services’ Health Resources and Service Administration and the CDC, produced a series of recommendations regarding the prevention, assessment, and treatment of child and adolescent overweight and obesity.

Four specific target behaviors were identified that are supported by consistent scientific evidence. These key target behaviors consist of :

1. Consuming at least five servings of fruits or vegetables each day
2.  Limiting screen time (TV, computer, and video games) to two hours or less per day
3. Engaging in at least one hour of physical activity per day
4. Consuming almost no sugary beverages

This approach is called the 5–2–1-0 intervention and is readily actionable. The message is easy to remember and reasonably easy to implement. Messaging has been adopted widely in regional initiatives, either directly or in a slightly modified form. It will be interesting to see how effective this and other prevention strategies will be.

It should be clear by now that the obesity pandemic cannot be brushed of as being healthy at any weigh. On the flip side weight bias and discrimination are unacceptable and health professionals need to learn how to address weight in a productive way. Based on this first module it should also be clear that the main emphasis needs be on obesity prevention and supporting families to make a healthy, active lifestyle the norm.

In the followong modules you will explore how lifestyle decisions starting before can put a child on a healthy or unhealthy trajectory in life.

Interested In More Information?

Fothergill E, Guo J, Howard L, et al. Persistent metabolic adaptation 6 years after “The Biggest Loser” competition. Obesity (Silver Spring). 2016;24(8):1612-1619. doi:10.1002/oby.21538

MacLean PS, Wing RR, Davidson T, et al. NIH working group report: Innovative research to improve maintenance of weight loss. Obesity (Silver Spring). 2015;23(1):7-15. doi:10.1002/oby.20967

Flanagan EW, Spann R, Berry SE, et al. New insights in the mechanisms of weight-loss maintenance: Summary from a Pennington symposium. Obesity (Silver Spring). 2023;31(12):2895-2908. doi:10.1002/oby.23905