Continuing Medical Education
Obesity and the skin: Skin physiology and skin manifestations of obesity

https://doi.org/10.1016/j.jaad.2006.12.004Get rights and content

Obesity is widely recognized as an epidemic in the Western world; however, the impact of obesity on the skin has received minimal attention. The purpose of this article is to highlight the association between obesity and dermatologic conditions. We review the impact of obesity on the skin, including skin physiology, skin manifestations of obesity, and dermatologic diseases aggravated by obesity. Obesity is responsible for changes in skin barrier function, sebaceous glands and sebum production, sweat glands, lymphatics, collagen structure and function, wound healing, microcirculation and macrocirculation, and subcutaneous fat. Moreover, obesity is implicated in a wide spectrum of dermatologic diseases, including acanthosis nigricans, acrochordons, keratosis pilaris, hyperandrogenism and hirsutism, striae distensae, adiposis dolorosa, and fat redistribution, lymphedema, chronic venous insufficiency, plantar hyperkeratosis, cellulitis, skin infections, hidradenitis suppurativa, psoriasis, insulin resistance syndrome, and tophaceous gout. We review the clinical features, evidence for association with obesity, and management of these various dermatoses and highlight the profound impact of obesity in clinical dermatology.

Learning objective

After completing this learning activity, participants should be aware of obesity-associated changes in skin physiology, skin manifestations of obesity, and dermatologic diseases aggravated by obesity, and be able to formulate a pathophysiology-based treatment strategy for obesity-associated dermatoses.

Introduction

Obesity is increasingly being recognized as a major public health problem in the United States. The prevalence of obesity, which is defined as a body mass index (BMI) of 30 kg/m2 or greater, has significantly increased among the US population over the past 30 years.1 Approximately 119 million Americans, nearly two thirds of adult Americans, are either overweight or obese.2 Recent research estimates that between one fourth and one third of American adults are obese,1, 2 and one in six children and adolescents is overweight.1 This increased prevalence of obesity has been noted among all age, gender, and racial groups in all 50 states.2

The total cost attributable to obesity in the United States in 1995 was estimated to amount to nearly $100 billion.3 More than $50 billion were direct medical costs, and over 60 million physician visits were attributable to obesity in 1994.3 It is widely recognized that obesity increases the risk of coronary heart disease, hypertension, hyperlipidemia, osteoarthritis, and diabetes. Obesity is also known to be directly related to increased risk of sleep apnea; breast, endometrial, and colon cancer; gallbladder disease; musculoskeletal disorders; severe pancreatitis, diverticulitis; infertility; urinary incontinence; and idiopathic intracranial hypertension.4 Obesity is indirectly related to anxiety, impaired social interaction, and depression.4 However, the impact of obesity on the skin has received minimal attention.

Obesity results from both environmental and genetic factors. Based on previous studies, approximately 60% to 70% of the variance in BMI can be attributed to environment and 30% to 40% of the variance in BMI can be attributed to genetics.5 The contributions of environmental factors to the etiology of obesity are well known. Dietary choices, socioeconomic status, and behavioral factors, such as inactivity, are all important factors in obese patients. In the United States, high-caloric food is cheap and abundant. Moreover, advances in technology both at home and in the workplace have dramatically reduced the amount of physical activity compared with previous generations. Obesity results from a chronic imbalance between food intake and energy expenditure. Specifically, 3 metabolic factors have been reported to be predictive of weight gain: (1) low adjusted sedentary energy expenditure6; (2) high respiratory quotient (carbohydrate-to-fat oxidation ratio)7; and (3) low level of spontaneous physical activity.

The interaction between genetics and environment is also important. Individuals may be genetically predisposed to become obese; however, the obesity genotype may only be expressed under certain environmental conditions. In Western countries, exposure to high-fat diets and sedentary lifestyle is common; thus the proportion of the population expressing the obesity genotype has increased.5

Although researchers have identified monogenic forms of obesity resulting from mutations in genes involved in central pathways of food intake regulation, the vast majority of obesity cases result from a complex polygenic disease involving interactions between multiple genes and the environment. The genetics of obesity is an ongoing topic of study and we refer the reader to the detailed reviews by Snyder et al8 and Cancello et al9 outlining the obesity gene map and various signaling molecules implicated in obesity. For the purpose of this review, we will focus on the two gene products which are known to have direct effects on the skin—the leptin and proopiomelanocortin (POMC) genes.

Leptin, the product of the Ob gene, is a hormone secreted by adipocytes that regulates energy homeostasis and food intake via specific receptors in the hypothalamus.10 Congenital leptin deficiency has been identified in humans and is associated with a rare, severe early-onset form of obesity.11 In such patients, treatment with leptin is successful.12 However, most obese patients actually have elevated circulating leptin levels in the setting of functional leptin resistance, and treatment with exogenous leptin is ineffective in ameliorating the obesity.13 Leptin receptors (Ob-R) have been located on tissues, including keratinocytes, fibroblasts, endothelial cells, and adipose tissue.14, 15, 16 Many studies have examined the beneficial role of leptin in wound healing. Leptin is acutely up-regulated in injured skin17 and in vitro promotes fibroblast proliferation and collagen synthesis.15 Leptin has also been shown to promote endothelial cell growth and angiogenesis, but at higher levels it proves toxic to vasculature, leading to capillary leakage and avascular zones. Decreased levels of leptin have also been shown in patients with some forms of lipodystrophy18; in mouse models of generalized lipodystrophy, administration of exogenous leptin increases glucose metabolism and restores insulin sensitivity. This suggests a possible role of leptin in the pathophysiology of this disorder as well as in the insulin resistance syndrome.19

The second possible genetic contributor towards obesity is the POMC gene. POMC is expressed in various tissues, including the pituitary, immune system, hypothalamus, and skin.20, 21 In these tissues, POMC is cleaved into smaller peptides including beta-endorphin, adrenocorticotropin, and alpha-, beta- and gamma-melanocyte stimulating hormones, which play various roles in control of analgesia, inflammation, adrenal steroidogenesis, and skin pigmentation.20, 22 The POMC-derived melanocortin peptides bind with different affinity and specificity to a set of 5 homologous melanocortin receptors.23 MC1 receptor is associated with human pigmentation and mutations in the gene for this receptor are known to cause red hair and fair skin.24 MC4r deficiency is the most common monogenic cause of obesity, and mutations in this gene affect at least 3% of extremely obese individuals.23, 25 This receptor appears to play a key role in the control of eating behavior in humans.26 A syndromic variant of POMC deficiency has been described with complete loss-of-function mutations of the POMC gene.23, 27, 28 The syndrome consists of severe early-onset obesity, adrenal insufficiency, reduced skin pigmentation, and red-orange hair. However, the contribution of the POMC gene to the pathogenesis of nonsyndromic obesity remains unclear.

Section snippets

Obesity and skin physiology

Obesity is related to a number of effects on skin physiology, including effects on skin barrier function, sebaceous glands and sebum production, sweat glands, lymphatics, collagen structure and function, wound healing, microcirculation and macrocirculation, and subcutaneous fat.

Skin manifestations of obesity

Obesity is associated with a number of dermatoses, including acanthosis nigricans, acrochordons, keratosis pilaris, hyperandrogenism and hirsutism, striae distensae, and adiposis dolorosa, and with fat redistribution (Table I).

Skin diseases aggravated by obesity

Skin diseases aggravated but not directly caused by obesity include lymphedema, chronic venous insufficiency, plantar hyperkeratosis, cellulite, skin infections, hidradenitis suppurativa, psoriasis, insulin resistance syndrome , and tophaceous gout.

Obesity and dermatologic pharmacology

Obesity is known to significantly affect both skin and systemic physiology. With growing numbers of obese patients, it will be increasingly important for dermatologists to be able to modify and adapt topical and systemic dermatologic therapies for obese patients. Common medications, such as oral isotretinoin and griseofulvin, require body weight–adjusted dosing; however, dermatologists often prescribe them in suboptimal doses for obese patients because of concerns about toxicity. In addition,

Conclusion

Although obesity is recognized as a major public health problem and is increasing in prevalence, little attention has been paid to the impact of obesity on the skin. Obesity is responsible for a variety of changes in skin physiology and is implicated in a wide spectrum of dermatologic diseases. Given the growing numbers of obese patients, dermatologists must work with primary care physicians and patients to reduce the detrimental effects of obesity on the skin.

References (206)

  • R.F. Morrison et al.

    Hormonal signaling and transcriptional control of adipocyte differentiation

    J Nutr

    (2000)
  • A.S. Avram et al.

    Subcutaneous fat in normal and diseased states: 2. Anatomy and physiology of white and brown adipose tissue

    J Am Acad Dermatol

    (2005)
  • M.M. Avram et al.

    Subcutaneous fat in normal and diseased states: 1

    Introduction. J Am Acad Dermatol

    (2005)
  • C.C. Grasinger et al.

    Vulvar acanthosis nigricans: a marker for insulin resistance in hirsute women

    Fertil Steril

    (1993)
  • M.I. Rendon et al.

    Acanthosis nigricans: a cutaneous marker of tissue resistance to insulin

    J Am Acad Dermatol

    (1989)
  • V.A. Akovbyan et al.

    Successful treatment of acanthosis nigricans with etretinate

    J Am Acad Dermatol

    (1994)
  • E. Muscelli et al.

    Differential effect of weight loss on insulin resistance in surgically treated obese patients

    Am J Med

    (2005)
  • K. Ruutiainen et al.

    Influence of body mass index and age on the grade of hair growth in hirsute women of reproductive ages

    Fertil Steril

    (1988)
  • S. Kang

    Topical tretinoin therapy for management of early striae

    J Am Acad Dermatol

    (1998)
  • B. Amine et al.

    Dercum's disease (adiposis dolorosa): a new case-report

    Joint Bone Spine

    (2004)
  • P. Petersen et al.

    Dercum's disease (adiposis dolorosa). Treatment of the severe pain with intravenous lidocaine

    Pain

    (1987)
  • S.E. Kahn et al.

    Obesity, body fat distribution, insulin sensitivity and Islet beta-cell function as explanations for metabolic diversity

    J Nutr

    (2001)
  • M.L. Baskin et al.

    Prevalence of obesity in the United States

    Obes Rev

    (2005)
  • F as in fat: how obesity policies are failing in America 2005. Trust for America's Health. Available at:...
  • A.M. Wolf et al.

    Current estimates of the economic cost of obesity in the United States

    Obes Res

    (1998)
  • F.X. Pi-Sunyer

    The obesity epidemic: pathophysiology and consequences of obesity

    Obes Res

    (2002)
  • E. Ravussin et al.

    Reduced rate of energy expenditure as a risk factor for body-weight gain

    N Engl J Med

    (1988)
  • F. Zurlo et al.

    Low ratio of fat to carbohydrate oxidation as predictor of weight gain: study of 24-h RQ

    Am J Physiol

    (1990)
  • E.E. Snyder et al.

    The human obesity gene map: the 2003 update

    Obes Res

    (2004)
  • J.M. Friedman et al.

    Leptin and the regulation of body weight in mammals

    Nature

    (1998)
  • C.T. Montague et al.

    Congenital leptin deficiency is associated with severe early-onset obesity in humans

    Nature

    (1997)
  • I.S. Farooqi et al.

    Effects of recombinant leptin therapy in a child with congenital leptin deficiency

    N Engl J Med

    (1999)
  • J.B. Fine et al.

    Leptin levels in obesity

    Int J Dermatol

    (1997)
  • S. Margetic et al.

    Leptin: a review of its peripheral actions and interactions

    Int J Obes Relat Metab Disord

    (2002)
  • P. Li et al.

    [Study on the effect of leptin on fibroblast proliferation and collagen synthesis in vitro in rats.]

    Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi

    (2005)
  • A. Murad et al.

    Leptin is an autocrine/paracrine regulator of wound healing

    FASEB J

    (2003)
  • V.C. Pardini et al.

    Leptin levels, beta-cell function, and insulin sensitivity in families with congenital and acquired generalized lipoatropic diabetes

    J Clin Endocrinol Metab

    (1998)
  • I. Shimomura et al.

    Leptin reverses insulin resistance and diabetes mellitus in mice with congenital lipodystrophy

    Nature

    (1999)
  • G.S. Yeo et al.

    The role of melanocortin signalling in the control of body weight: evidence from human and murine genetic models

    QJM

    (2000)
  • H. Krude et al.

    Obesity due to proopiomelanocortin deficiency: three new cases and treatment trials with thyroid hormone and ACTH4-10

    J Clin Endocrinol Metab

    (2003)
  • J.V. Schaffer et al.

    The melanocortin-1 receptor: red hair and beyond

    Arch Dermatol

    (2001)
  • R.D. Cone

    Haploinsufficiency of the melanocortin-4 receptor: part of a thrifty genotype?

    J Clin Invest

    (2000)
  • I.S. Farooqi et al.

    Clinical spectrum of obesity and mutations in the melanocortin 4 receptor gene

    N Engl J Med

    (2003)
  • H. Krude et al.

    Severe early-onset obesity, adrenal insufficiency and red hair pigmentation caused by POMC mutations in humans

    Nat Genet

    (1998)
  • L. Yaswen et al.

    Obesity in the mouse model of pro-opiomelanocortin deficiency responds to peripheral melanocortin

    Nat Med

    (1999)
  • H. Loffler et al.

    The influence of body mass index on skin susceptibility to sodium lauryl sulphate

    Skin Res Technol

    (2002)
  • C.C. Zouboulis et al.

    The human sebocyte culture model provides new insights into development and management of seborrhoea and acne

    Dermatology

    (1998)
  • L. Cordain

    Implications for the role of diet in acne

    Semin Cutan Med Surg

    (2005)
  • D. Deplewski et al.

    Growth hormone and insulin-like growth factors have different effects on sebaceous cell growth and differentiation

    Endocrinology

    (1999)
  • M. Cappel et al.

    Correlation between serum levels of insulin-like growth factor 1, dehydroepiandrosterone sulfate, and dihydrotestosterone and acne lesion counts in adult women

    Arch Dermatol

    (2005)
  • Cited by (0)

    Funding sources: None.

    Conflicts of interest: None declared.

    View full text