US Pharm. 2022;47(6):23-26.

ABSTRACT: Roughly two of every five U.S. men are classified as obese. Compared with females, males tend to carry more visceral fat in the belly, a condition also termed android obesity. This difference in the distribution of adipose tissue puts men at higher risk for harmful effects. More research is needed to clarify the complex etiology of the adverse health effects of excess visceral fat, but android obesity is known to increase the risk of adverse health effects in male patients, including insulin resistance, metabolic syndrome, cardiovascular complications, and other disorders. Lifestyle modifications are the foundation of reducing abdominal fat, and pharmacists can educate patients about behavioral and pharmacotherapeutic measures they can undertake to achieve this goal.

For every five men in the United States, roughly two are classified as obese, constituting 40% to 46% of the male population.1 Although the rate of obesity is similar in women, the distribution of adipose tissue in men is correlated with more harmful effects.2 A considerable share of the medical literature on body fat focuses on the differences in regional distribution of adipose tissue between the sexes and on the implications this distribution has on overall health. The body composition of females has more fat, whereas males have greater muscle mass.2-4 In women, fat deposits are typically in the lower body (i.e., gluteal-femoral region), known as gynoid obesity; men tend to develop belly fat (i.e., deposits in the abdominal region), termed android obesity.

Background

In the late 1900s, researchers postulated that the location of adipose tissue might have more deleterious effects on health than quantity alone.3,5 Android obesity, marked by enlarged waist circumference, was linked to an increased risk of metabolic and cardiovascular complications. At the same time, advances in radiographic imaging allowed for further subcategorization of regional adipose tissue as subcutaneous (in the deep layer of the skin; prevalent in gynoid obesity), visceral (surrounding internal organs; prevalent in android obesity), or ectopic (within internal organs).6 These advances led to greater insight into the harms of abdominal fat, particularly the association between abdominal visceral fat and poor health outcomes.

Measuring Body Fat

The standard for determining obesity is BMI, a measure that is based on a calculation of the patient’s weight and height.5,7 Although high BMI has been associated with poor health outcomes at certain percentiles, this measure does not provide insight on the composition of the extra weight. For this reason, other measures of body fat may be more accurate for determining health risks in male patients based on the presence of abdominal visceral fat. Skinfold thickness, bioelectrical impedance, underwater weighing, and dual-energy x-ray absorptiometry may equip healthcare providers with greater insight and aid in the recognition of patients who are normal weight, metabolically obese, or metabolically healthy obese.

Adverse Health Effects of Abdominal Visceral Fat

As with many aspects of medicine, the etiology of the adverse health effects of excess visceral fat is complex; the pathophysiology is unclear, and evidence on the variables involved is conflicting. Although obesity is a well-established risk factor for insulin resistance and type 2 diabetes as well as dyslipidemia, hypertension, cardiovascular disease, and other conditions, not all obese patients develop complications.8-10 However, visceral fat has been shown to increase the risk of developing a multitude of comorbidities.11-13

To understand the harm that visceral fat can cause, it must first be recognized that fat is not merely inert storage for excess calories but a metabolically active endocrine organ secreting a number of biologically active compounds. Adipocytes secrete both peptide chemical messengers called adipokines (or adipocytokines) and lipid chemical messengers known as lipokines.14,15 Evidence suggests that there are differences in the endocrine activities of visceral fat and subcutaneous fat.10,13,15 It has also been noted that adipose tissue is composed of not only adipocytes but also immune cells, including macrophages, monocytes, and endothelial cells.15 Among the adipokines secreted are tumor necrosis factor alpha and interleukin-6, which are believed to contribute to insulin resistance.16 This is in contrast to adiponectin (a signaling molecule responsible for maintaining insulin sensitivity), which is downregulated by accumulation of visceral adipose tissue.17

While the biochemical mechanisms described above aid in understanding the association between visceral fat, insulin resistance, and type 2 diabetes, research to elucidate other comorbidities is ongoing.18-20 Clear associations have been established between abdominal visceral fat and the presence of adverse health effects including metabolic syndrome, dyslipidemia, cardiovascular disease, hypertension, resistant hypertension, a prothrombotic state, progression of kidney disease, gout, and certain cancers.18,21-35 To distinguish general obesity from excess abdominal visceral fat, researchers have used CT and ultrasound to determine the ratio of visceral to subcutaneous fat and epicardial-fat thickness, respectively. For example, in one study that categorized patients with BMI-determined obesity into hypertensive and normotensive groups, the hypertensive group had a higher visceral-to-subcutaneous-fat ratio compared with the normotensive group that was statistically significant, even though the BMIs of the two groups did not differ significantly.24 Similar results were seen in studies evaluating resistant hypertension, venous thromboembolism, progression of kidney disease, and colorectal and breast cancers in women.

Reduction of Abdominal Visceral Fat

It has long been known that lifestyle modifications are the foundation of reducing abdominal fat. Diet and exercise serve as the most efficient strategies because visceral fat is more readily metabolized into fatty acids than is subcutaneous fat.36 However, many patients have difficulty maintaining dietary modifications and consistently engaging in physical activity to the degree necessary to eliminate abdominal fat.37 The following sections discuss various strategies for minimizing or preventing abdominal-fat accumulation.

Fitness: The mainstay of physical activity is exercise that targets waist circumference and muscle mass.36 The American Heart Association recommends that adults engage in at least 30 minutes of moderate-intensity exercise per day, or 150 minutes per week. Examples of moderate-intensity aerobic activities include brisk walks, biking at a pace less than 10 miles per hour, water aerobics, dancing, gardening, and sports such as tennis. Vigorous-intensity aerobic exercise is defined as at least 75 minutes per week of activities such as hiking uphill, running, swimming laps, biking at a pace greater than 10 miles per hour, and jumping rope.38 Although strength training may not cut pounds, incorporating it up to two times per week will help increase muscle mass and reduce abdominal fat.36,39 Patients should be advised that although spot exercises such as sit-ups will tighten abdominal muscles, they will not affect visceral-fat loss. Ultimately, any opportunity a patient can find to increase movement and activity through daily tasks will enhance the reduction of abdominal fat. Examples of daily tasks and activities that may afford such opportunities include parking farther away from entrances, taking the stairs instead of the elevator, and walking around while talking on the phone.36

Diet: Patients should consume a balanced diet comprising plant-based foods (e.g., vegetables, fruits, whole grains), lean sources of protein (e.g., fish, low-fat dairy), and moderate amounts of unsaturated fats (e.g., nuts, certain vegetable oils).39 Saturated fats (e.g., high-fat dairy, cheese, butter), processed meats, and simple carbohydrates (e.g., white bread, refined-grain pasta) should be avoided.39,40 Limiting alcohol intake is another way to minimize calories and abdominal-fat accumulation. Moderate alcohol intake equates to two drinks per day for men aged 65 years and younger and one drink per day for those older than age 65 years. Substituting water, with or without artificial sweeteners, for sugary drinks is helpful for reducing visceral fat.39 Portion size is just as important as what is eaten. The U.S. Department of Agriculture’s MyPlate resource (www.myplate.gov) is a patient-friendly guide on this topic. For patients who enjoy eating out, it is important to address how to recognize healthful options on a restaurant menu and to encourage meal-sharing or eating only half of the food and taking the other half home.

Smoking Cessation: Smoking leads to many health risks and problems, one of them being the accumulation of abdominal fat.36 The more a person smokes, the more prone he or she is to store fat in the abdomen rather than the hips and thighs. Assessing a patient’s readiness to quit smoking can help the pharmacist provide appropriate guidance on how to achieve better health.

Sleep: Poor sleep induces stress in the body and enhances the accumulation of visceral fat.36 In a longitudinal study, adult subjects younger than 40 years who slept 5 hours or less per night added significantly more visceral fat. However, oversleeping is not advantageous; in the same age group, subjects who slept more than 8 hours per night accumulated visceral fat as well. Establishing healthful bedtime routines in patients with poor sleep habits can greatly benefit their health. These patients should be encouraged to determine a set bedtime, turn off electronics within 30 minutes to 1 hour of sleep, refrain from eating just before bedtime, use the bedroom only for sleeping, and find ways to relax before going to sleep.

Pharmacotherapy: In addition to lifestyle modification, pharmacotherapy has proven effective for treating obesity; however, few studies have adequately investigated the effects of medications on visceral fat depots.37 Instead, many studies have examined changes in body weight or BMI as primary end points.41 A 2021 study assessing liraglutide’s effects on visceral and ectopic fat in overweight and obese adults demonstrated that a dosage of 3 mg once daily in conjunction with lifestyle modifications significantly lowered visceral adipose tissue over a 40-week period.37 Liraglutide, a glucagon-like peptide 1 (GLP-1) receptor agonist, works to induce glucose-dependent insulin secretion, reduce plasma glucagon concentrations, delay gastric emptying, and suppress appetite.37 Liraglutide was the first GLP-1 receptor agonist approved to treat obesity; another agent in this class, semaglutide, has recently been approved. Both medications are indicated for treatment of obesity in adults with a BMI of 30 kg/m2 or greater, or a BMI of 27 kg/m2 or greater with at least one weight-related morbidity. These agents are contraindicated in patients with a personal history of pancreatitis or a personal or family history of medullary thyroid cancer or multiple endocrine neoplasia 2A or 2B. Liraglutide is administered subcutaneously in the abdomen, thigh, or upper arm once daily at an initial dose of 0.6 mg and titrated weekly to 3 mg; treatment efficacy is measured by a weight loss of 4% or greater within 16 weeks of therapy. Semaglutide is administered subcutaneously at a maximum dosage of 2.4 mg once weekly; treatment efficacy is measured by a weight loss of 5% or greater.42 These agents demonstrate significant loss of visceral fat compared with other weight-loss medications that target appetite suppression and overall body weight.

Follow-up and Monitoring: Consistency is important. Once care has been individualized, monitoring the patient’s progress is essential to maintaining reductions in abdominal fat. Waist measurements correlate to the concentration of abdominal fat; for men, a waist measurement of more than 40 inches indicates an unhealthy concentration.40 It should be kept in mind that although liposuction and other cosmetic procedures may reduce the patient’s waist measurement, they target subcutaneous fat only and do not reduce visceral fat.36

Conclusion

Male patients who present with an unhealthy waist circumference or a general desire to lose belly fat and lead a healthier lifestyle may benefit from lifestyle modifications as well as certain therapeutic medications. Pharmacists can assist in the fight against obesity and obesity-related health outcomes by providing patients and healthcare professionals with appropriate education. Counseling patients on how to lose weight and conducting frequent motivational interviews are just two of the ways that pharmacists can help improve patient outcomes and contribute to reduced health-institution costs related to android obesity.

REFERENCES

1. Hales CM, Carroll MD, Fryar CD, Ogden CL. Prevalence of obesity and severe obesity among adults: United States, 2017–2018. NCHS Data Brief. 2020;(360):1-8.
2. Karastergiou K, Smith SR, Greenberg AS, Fried SK. Sex differences in human adipose tissues—the biology of pear shape. Biol Sex Differ. 2012;3(1):13.
3. Wajchenberg BL. Subcutaneous and visceral adipose tissue: their relation to the metabolic syndrome. Endocr Rev. 2000;21(6):697-738.
4. Blaak E. Gender differences in fat metabolism. Curr Opin Clin Nutr Metab Care. 2001;4(6):499-502.
5. Tchernof A, Després JP. Pathophysiology of human visceral obesity: an update. Physiol Rev. 2013;93(1):359-404.
6. Nauli AM, Matin S. Why do men accumulate abdominal visceral fat? Front Physiol. 2019;10:1486.
7. CDC. Body mass index: considerations for practitioners. www.cdc.gov/obesity/downloads/bmiforpactitioners.pdf. Accessed March 31, 2022.
8. Kanaya AM, Vaisse C. Obesity. In: Gardner DG, Shoback D, eds. Greenspan’s Basic & Clinical Endocrinology. 10th ed. New York, NY: McGraw Hill Education; 2018.
9. Powell-Wiley TM, Poirier P, Burke LE, et al. Obesity and cardiovascular disease: a scientific statement from the American Heart Association. Circulation. 2021;143(21):e984-e1010.
10. Pogodzinski D, Ostrowska L, Smarkusz-Zarzecka J, Zysk B. Secretome of adipose tissue as the key to understanding the endocrine function of adipose tissue. Int J Mol Sci. 2022;23(4):2309.
11. Huang PL. A comprehensive definition for metabolic syndrome. Dis Model Mech. 2009;2(5-6):231-237.
12. Bergman RN, Kim SP, Catalano KJ, et al. Why visceral fat is bad: mechanisms of the metabolic syndrome. Obesity (Silver Spring). 2006;14(suppl 1):S16-S19.
13. Masharani U, German MS. Pancreatic hormones and diabetes mellitus. In: Gardner DG, Shoback D, eds. Greenspan’s Basic & Clinical Endocrinology. 10th ed. New York, NY: McGraw Hill Education; 2018.
14. Scheja L, Heeren J. The endocrine function of adipose tissues in health and cardiometabolic disease. Nat Rev Endocrinol. 2019;15(9):507-524.
15. McGown C, Birerdinc A, Younossi ZM. Adipose tissue as an endocrine organ. Clin Liver Dis. 2014;18(1):41-58.
16. Sell H, Eckel J, Dietze-Schroeder D. Pathways leading to muscle insulin resistance—the muscle-fat connection. Arch Physiol Biochem. 2006;112(2):105-113.
17. Coelho M, Oliveira T, Fernandes R. Biochemistry of adipose tissue: an endocrine organ. Arch Med Sci. 2013;9(2):191-200.
18. Matsuzawa Y, Shimomura I, Nakamura T, et al. Pathophysiology and pathogenesis of visceral fat obesity. Obes Res. 1995;3(suppl 2):S187-S194.
19. Klein S. Is visceral fat responsible for the metabolic abnormalities associated with obesity?: implications of omentectomy. Diabetes Care. 2010;33(7):1693-1694.
20. Gastaldelli A, Miyazaki Y, Pettiti M, et al. Metabolic effects of visceral fat accumulation in type 2 diabetes. J Clin Endocrinol Metab. 2002;87(11):5098-5103.
21. Després JP. Obesity and cardiovascular disease: weight loss is not the only target. Can J Cardiol. 2015;31(2):216-222.
22. Després JP. Body fat distribution and risk of cardiovascular disease: an update. Circulation. 2012;126(10):1301-1313.
23. Liu J, Fox CS, Hickson DA, et al. Impact of abdominal visceral and subcutaneous adipose tissue on cardiometabolic risk factors: the Jackson Heart Study. J Clin Endocrinol Metab. 2010;95(12):5419-5426.
24. Kanai H, Matsuzawa Y, Kotani K, et al. Close correlation of intra-abdominal fat accumulation to hypertension in obese women. Hypertension. 1990;16(5):484-490.
25. Jordan J, Grassi G. Belly fat and resistant hypertension. J Hypertens. 2010;28(6):1131-1133.
26. Hotoleanu C. Association between obesity and venous thromboembolism. Med Pharm Rep. 2020;93(2):162-168.
27. Bureau C, Laurent J, Robic MA, et al. Central obesity is associated with non-cirrhotic portal vein thrombosis. J Hepatol. 2016;64(2):427-432.
28. Ageno W, Di Minno MN, Ay C, et al. Association between the metabolic syndrome, its individual components, and unprovoked venous thromboembolism: results of a patient-level meta-analysis. Arterioscler Thromb Vasc Biol. 2014;34(11):2478-2485.
29. Goldhaber SZ, Grodstein F, Stampfer MJ, et al. A prospective study of risk factors for pulmonary embolism in women. JAMA. 1997;277(8):642-645.
30. Mazzoccoli G, Dagostino MP, Grilli M, et al. Idiopathic deep venous thrombosis and epicardial fat thickness: the age, gender and obesity connection. Biomed Aging Pathology. 2011;1(3):175-178.
31. Mazzoccoli G, Copetti M, Dagostino MP, et al. Epicardial adipose tissue and idiopathic deep venous thrombosis: an association study. Atherosclerosis. 2012;223(2):378-383.
32. Manabe S, Kataoka H, Mochizuki T, et al. Impact of visceral fat area in patients with chronic kidney disease. Clin Exp Nephrol. 2021;25(6):608-620.
33. Lee J, Lee JY, Lee JH, et al. Visceral fat obesity is highly associated with primary gout in a metabolically obese but normal weighted population: a case control study. Arthritis Res Ther. 2015;17(1):79.
34. Lee JY, Lee HS, Lee DC, et al. Visceral fat accumulation is associated with colorectal cancer in postmenopausal women. PLoS One. 2014;9(11):e110587.
35. Le Marchand L, Wilkens LR, Castelfranco AM, et al. Circulating biomarker score for visceral fat and risks of incident colorectal and postmenopausal breast cancer: the Multiethnic Cohort Adiposity Phenotype Study. Cancer Epidemiol Biomarkers Prev. 2020;29(5):966-973.
36. Harvard Health. Taking aim at belly fat. www.health.harvard.edu/staying-healthy/taking-aim-at-belly-fat. Accessed March 29, 2022.
37. Neeland IJ, Marso SP, Ayers CR, et al. Effects of liraglutide on visceral and ectopic fat in adults with overweight and obesity at high cardiovascular risk: a randomised, double-blind, placebo-controlled, clinical trial. Lancet Diabetes Endocrinol. 2021;9(9):595-605.
38. American Heart Association. American Heart Association recommendations for physical activity in adults and kids. www.heart.org/en/healthy-living/fitness/fitness-basics/aha-recs-for-physical-activity-in-adults. Accessed March 29, 2022.
39. Mayo Clinic. Belly fat in men: why weight loss matters. www.mayoclinic.org/healthy-lifestyle/mens-health/in-depth/belly-fat/art-20045685. Accessed March 29, 2022.
40. Harvard Health. Abdominal fat and what to do about it. www.health.harvard.edu/staying-healthy/abdominal-fat-and-what-to-do-about-it. Accessed March 29, 2022.
41. Gadde KM, Heymsfield SB. Targeting visceral adiposity with pharmacotherapy. Lancet Diabetes Endocrinol. 2021;9(9):551-552.
42. Perreault L. Obesity in adults: drug therapy. UpToDate. Waltham, MA: UpToDate Inc. www.uptodate.com. Accessed March 29, 2022.

The content contained in this article is for informational purposes only. The content is not intended to be a substitute for professional advice. Reliance on any information provided in this article is solely at your own risk.

To comment on this article, contact rdavidson@uspharmacist.com.