Abdominal obesity and metabolic syndrome: A cause and consequence affecting the lifespan

Highlights:

• Abdominal obesity results from insulin resistance and other factors that are a consequence of the metabolic syndrome
• Proinflammatory mediators released from the extra adipose tissue are responsible for the majority of adverse outcomes associated with metabolic syndrome
• Waist circumference, even with normal body mass index, is a risk factor for metabolic syndrome

Introduction

Metabolic syndrome is a collective term that describes a cluster of conditions, including diabetes, hypertension, and obesity. These disorders increase the risk of death from stroke and heart diseases, among other conditions. According to literature, abdominal obesity is a cause and consequence of metabolic syndrome. Evidence suggests that abdominal adiposity (accumulation of fat) is strongly linked to insulin resistance, dyslipidemia, and inflammation. The outcome of these pathologies is the development of cardiovascular diseases (CVDs), increased risk of various cancers, and metabolic syndrome. This leads to the premature development of the abovementioned age-related conditions, leading to earlier and higher mortality rates.

How visceral obesity influences metabolic syndrome and a myriad of conditions

According to studies, metabolic syndrome increases the risk of coronary heart disease, cerebrovascular disorders, and all-cause mortality by 2-fold for the first two and 1.5-fold for the latter, respectively (1). Abdominal obesity is the most frequently observed consequence of metabolic syndrome, making it a significant public health challenge. Research highlights the importance of measuring waist circumference rather than the body mass index (BMI) only to screen for individuals at risk of developing metabolic syndrome (2). This is because evidence suggests that people with excess visceral adiposity and any given amount of total body fat are at a substantially higher risk of having insulin resistance and other features of metabolic syndrome. This information was validated by studies that found individuals with high or low subcutaneous fat accumulation did not differ in insulin sensitivity, unlike those with increased visceral adiposity who demonstrated insulin resistance (2, 3). The previous does not dilute the value of BMI as a marker in determining overweight/obesity, as having a high BMI predisposes individuals to a risk of developing the said disorders regardless of waist circumference.  

It is important to understand that not all types of increased waistline pose the same risk of developing metabolic syndrome and related consequences. Research has mentioned that subcutaneous abdominal fat accumulation is not as dangerous as excessive visceral fat (3). The latter has been characterized as the worst metabolic profile due to its negative influence on overall health. Therefore, relying on waist circumference alone cannot be a reliable indicator to distinguish between subcutaneous and visceral obesity, thus the risk of metabolic syndrome. It is best to guide BMI measurement with waist circumference to obtain reliable results that help identify, to a certain extent, visceral obesity (3). Imaging techniques, like magnetic resonance imaging and dual-energy X-ray absorptiometry, can be used for more accurate results, while other methods, like bioelectric impedance, give less accurate results (4). To put things into perspective, a normal BMI is 18.5–24.9 kg/m2, which corresponds to a waist circumference of ≥80 cm2 for females and ≥90 cm for males (5). An additional 10 cmto the stated figures are where overweight starts. It is important to note that these numbers are also influenced by ethnicity and race.

The impact of waist circumference on health does not stop there. Research from major trials such as the INTERHEART found that higher waist-to-hip circumference (a marker of abdominal fat) was associated with an increased risk of myocardial infarction (3). Other studies also discussed the impact of the said marker on congestive heart disease (CHD) and highlighted that increased waist circumference was associated with an elevated CHD risk.

Inflammation as a central player in pathologies related to visceral obesity and metabolic syndrome

Chronic global inflammation is one of the common features of metabolic syndrome. It is believed that the main driver of this systemic inflammation is the excess adipose tissue, leading to increased oxidative stress and overactivity of the nuclear factor-κB (NF-κB) pathway (a pathway that plays a role in the expression of proinflammatory mediators, like cytokines and chemokines, among others) (6). This global inflammation is characterized by elevated levels of biomarkers like C-reactive protein, an acute-phase reactant protein. Another pathway involved in metabolic syndrome-related inflammation is the transcription factor AP-1 (activated protein 1 is a regulator of gene expression in response to stimuli, like cytokines, oxidative stress, and fatty acids) (6). Pathways involving 5′ AMP-activated protein kinase (AMPK) (an enzyme that plays a role in energy metabolism in the muscle) have also been suggested to play a role in metabolic syndrome. In this context, AMPK activation has been linked to improved glucose levels and reduced plasma lipids and intra-abdominal fat mass. This pathway has also been suggested to reduce oxidative stress by promoting nitric oxide synthase (an enzyme involved in the production of nitric oxide, which is important for insulin secretion in addition to playing other roles). Under obesity conditions, AMPK activation tends to be reduced.

With an internal environment supporting inflammation, mediators that play a role in inflammation are secreted by endothelial cells. Examples of these inflammatory cytokines include interleukin-6 (IL-6), IL-1, and tumor necrosis factor-alpha (TNF-α) (6-8). The literature suggests that TNF-α expression increases in adipocytes of obese individuals, influencing insulin sensitivity through the insulin receptor. Regarding IL-6, evidence suggests that its expression is increased under states of hyperinsulinemia, which is encountered with obesity, thereby stimulating the production of inflammatory proteins. However, research shows that its effect on insulin is tissue-specific, as IL-6 increases insulin sensitivity in skeletal muscles. In addition to the previous, there is a decrease in adiponectin levels, which is an adipokine (a signaling molecule produced by the adipose tissue and plays a role in energy and metabolism) with a protective role against atherosclerosis (9). Studies suggest that NF-κB and TNF-α activity is attenuated by the said adipokine (6). The abovementioned inflammatory mediators contribute to the development of type 2 diabetes, dyslipidemia, and cardiovascular disorders. Other adipokines that have been suggested to have a proinflammatory role is leptin (when expressed in excess); however, its role is not fully understood.

Abdominal obesity, metabolic syndrome, and longevity: Connecting the dots

The risk of developing diseases increases with age. By now, we have established abdominal obesity as a cause and outcome of metabolic syndrome, a consequence of the aging process. In the same context, biological processes of aging and cellular senescence are accelerated in metabolic syndrome (10). This means that the risk for chronic age-related disorders will increase, developing at earlier stages of life, reducing the functional capacity and quality of life (10, 11). In addition to the previous, obesity and metabolic syndrome have been linked to shorter life expectancy (12, 13). It is important to note that the majority of conditions caused by metabolic syndrome can be delayed or even prevented with lifestyle modifications, promoting longevity. Many studies have argued the benefits of reducing waist circumference to promote a longer lifespan, as it reduces the speed of processes arising from aging.

The main driver of the aging process is inflammation (inflammaging). The latter has already been linked to excess adipose tissue due to the release of cytokines that promote inflammation (12). In addition, obesity has been linked to the disturbance of cytokines that help regulate weight and appetite, therefore further complicating the process. Hormonal disruption has also been suggested to be influenced by obesity (12, 14). For example, the growth hormone, which is responsible for body composition and strength, has been found to be reduced in obese individuals. Research has highlighted that this reduction in growth hormone is similar to what is encountered with the aging process, where it decreases after the third decade of life.

Exercise and diet as mean to reduce visceral fat and control metabolic syndrome

Exercise and diet are among the most effective interventions that help reduce weight and increase lean body mass to reduce the risks associated with visceral fat and obesity (15, 16). Generally, diet therapy is the most effective technique to decrease weight and total fat mass in the body compared to exercise or medications because its effect results from negative energy balance (energy expenditure more than caloric intake). To achieve the latter objective, dietary goals should include avoiding sugary drinks, fast, and highly processed food because of high energy and adding healthy choices like fruits and vegetables.

It is important not to underestimate the effectiveness of exercise, especially the aerobic type, where its efficacy has been proven across multiple meta-analyses (15). In the same context, the benefits obtained from resistance training have also been highlighted in the literature, where significant benefits were seen when combined with a diet containing a sufficient amount of protein. Literature highlights that both aerobic and resistance training should be combined for best results. This is also supported by recommendations from the World Health Organization (17).

Tips

• Ensure that your client/patient understands that their BMI could be normal, yet their waist circumference could be high. This will put them at risk of developing metabolic syndrome and related consequences.
• Recommend performing regular blood checkups, as they can help identify problems at early stages and can also be used to monitor progress.
• Explain to your clients that their energy balance needs to be negative (more energy expenditure) to lose weight.
• Highlight the importance of physical activity and mention that studies suggest that exercise could potentially help reduce BMI and fat mass and increase basal metabolic rate and lean body mass.
• Recommend aerobic exercises, like brisk walking or light jogging, combined with strengthening training, like weight lifting, to obtain the best results. The recommended training frequency to get the best outcome is four sessions per week, with 50 minutes per session.
• Mention the importance of diet as a cornerstone in losing visceral fat and reducing the overall body fat mass. Encourage avoiding fast food and sugary drinks (they have high energy density and low ability to satiate) and advise to add more fruits, vegetables, and whole-grain foods.

Conclusions

Metabolic syndrome is a term that describes several conditions with an outcome that leads to reduced longevity. Abdominal adiposity is a cause and consequence of metabolic syndrome that arises from insulin resistance and other reasons. These conditions impact health through excessive release of proinflammatory mediators from the additional adipose tissue. This leaves individuals liable for the early development of age-related diseases. Waist circumference is an important indicator of metabolic syndrome and should be used in conjunction with BMI. 

References

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