Weight management is a complex interplay of various factors, with hormones playing a crucial role in regulating body fat storage, appetite, and metabolism. Understanding the intricate relationship between hormones and weight loss is essential for developing effective and sustainable weight management strategies. This article delves into the research surrounding key hormones involved in weight regulation and explores lifestyle modifications that can positively influence their balance.
The Hormonal Symphony of Weight Regulation
Several hormones act as key players in the regulation of body weight and fat storage. These include:
Leptin: Produced in body fat, leptin acts as a messenger to the brain, signaling the amount of body fat present. A common problem in obesity is “Leptin Resistance”, where the leptin level is high but it is not causing weight loss as it should. When we gain weight, our leptin level goes up, reducing appetite and promoting energy expenditure for weight loss. Conversely, weight loss leads to decreased leptin levels, increasing appetite and slowing metabolism.
Amylin: This hormone, produced in the pancreas, decreases food intake. Research suggests it may also reduce leptin resistance, promoting weight loss.
Ghrelin: Secreted primarily by the stomach, ghrelin is known as the "hunger hormone," driving us to eat. Skipping meals causes ghrelin levels to spike, potentially leading to overeating at the next meal. Carbohydrates are the most effective macronutrient to lower our ghrelin level. Protein is less effective but works to keep ghrelin suppressed for longer.
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GLP-1 (Glucagon-like peptide-1): GLP1 is one of several “nutrient sensing” fullness hormones produced in the intestine when we eat. Released from the intestine upon eating, GLP-1 promotes feelings of fullness and satisfaction, signaling the body to stop eating. It also plays a role in managing sugar levels. Individuals vary in how much hormone they produce, making it easy or more difficult to determine fullness and satisfaction. When ghrelin is high, we produce less GLP1, making us eat more food.
Glucagon: Produced in the pancreas when blood sugar levels are low, glucagon helps restore normal sugar levels by prompting the liver to release stored sugar. This extends the time between meals and suppresses appetite, favoring weight loss.
Insulin: Also released by the pancreas, insulin is the primary hormone regulating blood sugar levels, delivering sugar to organs for normal function. While it can influence hunger and fullness, its effects are complex and depend on interactions with other hormones. High insulin levels can cause, and be caused by, obesity leading to weight gain.
Cortisol: The adrenal glands produce cortisol, often called the "stress hormone," in response to stress.
Thyroid Hormones: The thyroid gland produces hormones that regulate metabolism. Thyroid conditions affecting hormone production can lead to weight gain or loss.
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Weight Loss Interventions and Appetite-Regulating Hormones
Weight loss can induce changes in appetite-regulating hormone levels, possibly linked to increases in appetite and weight regain. However, hormonal changes vary across interventions. A combined lifestyle intervention (CLI) may be essential to counteract the disease (GBD 2015 Obesity Collaborators, 2017; Chooi et al., 2019).
In clinical practice, very-low-energy diets are commonly used as they can induce substantial weight loss in a short amount of time (Mustajoki and Pekkarinen, 2001). However, hypocaloric diets are often accompanied by increases in self-reported appetite and followed by weight regain, making long-term weight loss maintenance a critical issue in obesity treatment (Mustajoki and Pekkarinen, 2001; Sumithran et al., 2011).
This commonly observed recidivism in response to diet-induced weight loss has been partly attributed to a physiological compensatory ‘starvation’ response, ranging from a more orexigenic (appetite-inducing) hormonal profile to increased metabolic efficiency favoring energy storage (Sumithran et al., 2011; Sumithran and Proietto, 2013; Greenway, 2015; Lean and Malkova, 2016).
The Impact of a Combined Lifestyle Intervention (CLI)
A 1.5-year combined lifestyle intervention (CLI) for obesity comprises a healthy diet, exercise, and cognitive behavioral therapy (CBT). The study subjects included adult patients with lifestyle-induced obesity who underwent a multidisciplinary CLI between October 2013 and October 2019. Exclusion criteria were other causes of obesity (e.g. genetic or endocrine diseases), inability to speak Dutch, intellectual disability (IQ < 80), current wish for pregnancy and severe physiological or behavioral problems impeding functioning in a group. An inclusion criterion was the presence of ≥1 obesity-related comorbidity (e.g., dyslipidemia, hypertension, non-alcoholic fatty liver disease, type 2 diabetes, obstructive sleep apnea or osteoarthritis).
Twice a year groups of 10-12 participants started a 1.5-year CLI trajectory. Every group session comprised 1.5 h of combined CBT and nutritional advice which were followed by 1.5 h by exercise sessions. The nutrition education protocol focused on promoting a well-balanced healthy diet in accordance with the Dutch food dietary guideline (Voedingscentrum, 2015), whereby participants were instructed not to follow a low-calorie diet scheme (therefore, we refer to the diet as ‘normocaloric’). The psychoeducational sessions were based on CBT and aimed to improve (stress-)coping, impulsivity, self-confidence and usage of the social support system.
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The nutrition and psychoeducation sessions were followed by 1.5 h of exercise. The exercise sessions comprised both aerobic endurance training as well as anaerobic resistance training. The aim was to stimulate exercise in the home-setting and to improve cardiorespiratory fitness and muscle strength.
Hormonal Changes Observed During CLI
Initial weight loss was maintained at 1.5 years (−5.0%, p < 0.001), and accompanied by decreased leptin and insulin levels at both 10 weeks and 1.5 years (all p < 0.05) compared to baseline. Most short-term signals were not affected. Only PP levels were decreased at 1.5 years compared to baseline (p < 0.05). CLI-induced weight loss was associated with changes in levels of long-term adiposity-related hormones towards healthy levels, but not with orexigenic changes in most short-term appetite signals. The clinical impact of alterations in appetite-regulating hormones during modest weight loss remains questionable.
Normalizations of the long-term adiposity-related hormones leptin, insulin and (HMW) adiponectin levels have been described consistently across different weight loss modalities (Lean and Malkova, 2016; Khosravi-Largani et al., 2019). However, findings are less consistent for short-term regulators of energy balance. Hypocaloric (very-low-energy) diets seem to induce weight-regain-favoring hormonal alterations (Essah et al., 2010; Sumithran et al., 2011; Greenway, 2015; Lean and Malkova, 2016). In contrast, results from exercise intervention studies rather point towards increased satiety signaling (Lean and Malkova, 2016; Sheikholeslami-Vatani and Rostamzadeh, 2022).
Weight Loss and Neurotensin
Weight loss led to decreased amount of the hormone neurotensin. People who have undergone bariatric surgery to lose weight release more neurotensin when they eat. People who live with obesity are leptin resistant, which means that they do not respond with weight lose to the hormone.
The Effects of Diet and Exercise on Sex Hormones
Losing just 5 percent or more of one’s weight could cut by a quarter to a half the risk for the most common, estrogen-sensitive breast cancers. Epidemiologists have long noted a link between obesity and increased risk of postmenopausal breast cancer.
The amount of weight lost was key to changes in hormone levels. The biggest effect was through diet plus exercise; exercise by itself didn’t produce much of a change in weight or estrogen. However, exercise prevents loss of muscle and bone, and it helps keep off the weight long term. Losing weight through a healthy diet that included reducing calories, reducing fat, and increasing vegetables, fruits and fiber significantly lowers blood estrogen levels in postemenopausal women.
The results of the study also could be relevant to overweight women who take breast cancer prevention drugs such as tamoxifen, raloxifene, and exemestane, which either block the action of estrogen or stop its production.
Lifestyle Strategies for Hormonal Balance and Weight Management
Recognizing the influence of lifestyle on hormone levels is crucial for effective weight management. Health-focused lifestyle choices can improve the balance of these hormones. These include:
Dietary Modifications: Eating three to four balanced meals a day that include fruits, vegetables, lean proteins, and healthy fats. Emphasizing fiber-rich foods and minimizing processed foods can positively impact hormone levels.
Regular Meal Timing: Eating three times a day can help regulate ghrelin levels and prevent overeating.
Physical Activity: Increasing muscle health with physical activity.
Sleep Optimization: Establishing a consistent, quality sleep routine can increase leptin levels. Improving the timing and quantity of sleep.
Stress Management: Learning stress relieving activities can optimize each of these hormone levels.
The Broader Perspective: Obesity and Public Health
The increasing prevalence of obesity challenges healthcare providers worldwide to counteract the disease. Understanding how hormones play a part in achieving and maintaining a healthy weight is only part of the picture. For best results, focus on the lifestyle changes you can make to improve your overall health, including your weight. Today, in many countries, half of the population live with overweight, and the number is increasing. Many people successfully lose weight.
The estimated prevalence of obesity in the USA is 72.5 million adults with costs attributed to obesity more than 147 billion dollars per year. Though caloric restriction has been used extensively in weight control studies, short-term success has been difficult to achieve, with long-term success of weight control being even more elusive. Therefore, novel approaches are needed to control the rates of obesity that are occurring globally.
The Impact of Macronutrients on Hormones
The macronutrient composition of meals is one variable that may contribute to excessive caloric intake under ad libitum conditions resulting in unwanted weight gain and the onset of obesity. The postprandial endocrine response associated with meals of varying macronutrient proportions may give some insight as to why certain food combinations lead to greater satiety resulting in less caloric ingestion than others. Identifying and exploiting the macronutrient proportions that are associated with satiety and favorable postprandial endocrine responses may be a useful strategy for initiating weight loss through appetite regulation in the absence of purposeful calorie restriction.
Macronutrient Proportions and Hormonal Response
Both exogenous insulin administration and endogenous postprandial insulin response have resulted in suppression of ghrelin. In addition, faulty regulation of ghrelin suppression is associated with insulin resistance. Postprandial ghrelin suppression has also been shown to be proportional to meal calorie content, and this association of meal calorie content with ghrelin suppression is reduced in obese individuals. Generally, obese individuals exhibit lower fasting ghrelin levels than their normal-weight counterparts which suggests that it may not be the initial amount of plasma ghrelin that regulates appetite but the magnitude and duration of postprandial ghrelin suppression and its ensuing rise to fasting levels.
The fat, protein, and carbohydrate compositions of meals have differing effects on ghrelin suppression as well as appetite regulation and satiety. Ingestion of a high-carbohydrate meal (77% energy) more effectively suppressed ghrelin and appetite compared to ingestion of a high-fat meal (75% energy) in nonobese women.
Based on the results of these studies, isocalorically increasing the proportion of fat calories in relation to calories from carbohydrates and proteins is not a viable strategy to decrease appetite and ad libitum calorie ingestion.
The Role of Protein
Numerous studies provide evidence that supports the use of a high-protein diet to induce appetite suppression and decreased ad libitum energy intake. Weigle et al. [20] reported that an increase of protein from 15% to 30% of dietary intake resulted in a decrease of ad libitum caloric intake and weight loss. These effects were evident in the absence of ghrelin suppression. The likely mechanism of action of high-protein diets on appetite suppression and decreased caloric intake may be outside of the control of ghrelin.
The Importance of Carbohydrates
In a recent study of healthy Pima Indians, higher plasma insulin responses were associated with a decrease in subsequent carbohydrate consumption and less weight gain. These results further point to insulin as a regulator of calorie consumption.
In conclusion, evidence tends to suggest that for the regulation of ad libitum caloric ingestion, a high-protein diet (~30% of total calories) may be beneficial whereas high-fat diets should most likely be avoided. It would appear to be most beneficial if the additional protein is ingested from solid food sources as food form also appears to play a role in feelings of satiety.
Meal Frequency and Hormones
Another factor associated with weight control that may not necessarily have a concomitant decrease in caloric intake is meal frequency. Caloric intake can be affected by caloric density in food, total energy consumption as well as meal frequency, but Solomon et al. [32] suggests that feeding frequency has received the least amount of empirical research. Additionally Stote et al. [33] most recently reported that nutrient-dense and low-calorie diets have received significant attention with regards to weight control and health outcomes, but the influence of meal frequency is yet to be firmly established.
To date evidence suggests that less frequent meal consumption with a large bolus of calories at each meal can lead to increases in adipose tissue [34]. Conversely consuming the same amount of calories with more frequent and smaller meals does not seem to impact the deposition of fat. Additionally Solomon et al. [32] report an increase in snacking has positive associations with BMI, but also with caloric intake, suggesting the need for studies involving meal frequency and weight control.
There have been some published findings regarding meal frequency and its effects on preprandial and postprandial satiety and gastric sensations of “fullness” or “emptiness” with some studies suggesting hormones may play a direct or indirect role [35]. These hormonal effects may primarily be related to ghrelin and insulin and possibly cortisol.
Hormonal Changes After Weight Loss
Altered appetite-related gut hormone concentrations may reflect a physiological adaptation facilitating weight regain after weight loss. A systematic search of PubMed (MEDLINE), EMBASE, SPORTDiscus, Cochrane Library, Web of Science, and ClinicalTrials.gov was conducted to identify randomised controlled trials (RCTs) and non-RCTs reporting in a fasting state either pre- and post-intervention appetite-related hormone concentrations or the changes therein after weight loss. The hormones examined were ghrelin, peptide tyrosine tyrosine (PYY), glucagon-like peptide -1 (GLP-1), and cholecystokinin (CCK), in their total and/or active form.
In response to weight loss induced by CR, EX or CREX, the meta-analysis revealed an increase in total ghrelin from both RCTs (SMD: 0.55, 95% CI: 0.07-1.04) and non-RCTs (SMD: 0.24, 95% CI: 0.14-0.35). A decrease in acylated ghrelin was identified for RCTs (SMD: -0.58, 95% CI: -1.09 to -0.06) but an increase was observed for non-RCTs (SMD: 0.15, 95% CI: 0.03 to 0.27). Findings also revealed a decrease in PYY (total PYY: SMD: -0.17, 95%CI: -0.28 to -0.06; PYY3-36: SMD: -0.17, 95%CI: -0.32 to -0.02) and active GLP-1 (SMD: -0.16, 95% CI: -0.28 to -0.05) from non-RCTs. Changes in hormones did not differ among the three interventions when controlling for weight loss. Meta-regression indicated that greater weight loss was associated with a greater increase in total ghrelin.
Weight loss induced by CR, EX, or CREX elicits an increase in total ghrelin, but varied responses in other appetite-related hormones.