With the introduction of effective antiretroviral therapy, HALS has become one of its most important long-term adverse effects [ 26 ]. HALS includes subcutaneous fat loss lipoatrophy , fat accumulation lipohypertrophy , or a combination of both Fig.

These morphologic abnormalities can also be associated with disorders of glucose and lipid metabolism. A year-old man with HALS. a Axial T2-weighted and b sagittal T1-weighted images show subcutaneous lipohypertrophy on the posterior neck arrows. Marked loss of subcutaneous fat including buccal fat pad is shown in the face arrowheads.

c Volume-rendered three-dimensional reformation image shows apparent concave cheeks and periorbital hollowing. Lipoatrophy manifests as a loss of fat mainly in the face, limbs, and buttocks [ 27 ]. The main risk factor for lipoatrophy is exposure to thymidine analog nucleoside reverse transcriptase inhibitors NRTIs , which today, however, are no longer the first-line drugs resorted to [ 27 ].

Dyslipidemia and insulin resistance frequently co-exist in this condition. Risk factors for the development of fat deposition include increasing age, female sex, elevated baseline triglycerides, and higher body fat percentage [ 29 ].

Abnormal reaction of subcutaneous fat to insulin injection is well known as lipohypertrophy and lipoatrophy. Insulin lipohypertrophy shows a tumor-like swelling of fatty tissue at the injection site due to the lipogenic effect of insulin Fig.

Growth hormone receptor antagonist is also reported to be a cause of lipohypertrophy at the injection site [ 30 ]. Lipoatrophy, which is considered to be an immune complex-mediated inflammatory lesion, rarely occurs today since the advent of recombinant human insulin and insulin analogs [ 31 ].

Lipohypertrophy remains a frequent complication of insulin therapy, reportedly in Injection into lipohypertrophied sites may contribute to poor glycemic control due to an erratic absorption of the drug.

A year-old man with type I diabetes and insulin injection lipohypertrophy. a CT image at the level of belly button shows bilateral localized subcutaneous fat deposition on the anterior abdominal wall arrows. b Volume-rendered three-dimensional reformation image show bilateral bulging of abdominal wall reflecting the insulin lipohypertrophy.

MSL has a strong association with heavy alcohol intake. Alcohol cessation and weight control are recommended although they do not reverse or stop the course of the disease [ 35 ]. MSL is also found in non-alcoholics in association with mitochondrial DNA mutations [ 36 ].

A defect of adrenergic stimulated lipolysis or mitochondrial disorder of brown fat tissue has been considered as the etiology of this disease in recent studies [ 37 ].

A year-old man with multiple symmetrical lipomatosis with sleep apnea. a Axial T2-weighted and b T1-weighted image show abnormal subcutaneous fat deposition in the anterior arrows and posterior neck asterisks. Note the increase of adipose tissue also observed in the posterior pharyngeal space small arrows.

Subcutaneous fat volume in the anterior neck is markedly decreased arrows , whereas in contrast, the fat deposition in the posterior neck has worsened asterisk. Suprascapular and supraclavicular involvement is common and tracheal or esophageal compression due to deep space-occupying lesions is a life-threatening complication [ 38 ].

CT is the optimal modality to evaluate deep-seated fat accumulation. Palliative removal of fatty tissue by surgical resection or liposuction and by injection lipolysis is recommended when symptomatic.

Adipocytes from VAT are more insulin-resistant compared with SCAT. The amount of visceral fat is a striking factor underlying the enhanced cardiovascular risk seen in this condition and is mediated by insulin resistance [ 40 , 41 ].

Central obesity can also induce hypertension through increased activity of adipose tissue renin-angiotensin-aldosterone system, sympathetic activation, and other mechanisms connected with insulin resistance. A year-old man with Cushing disease.

Note the enlarged sella due to pituitary macroadenoma arrowhead. c CT scanogram shows characteristic central obesity. d CT image at the level of bilateral renal hilum shows marked visceral fat deposition, in contrast to subcutaneous fat thinning boxed arrows.

The extremities are usually spared and may be wasted. Fat can also accumulate in the supraclavicular fossa, spinal canal spinal epidural lipomatosis , cheeks moon face , or dorsocervical fat pad buffalo hump [ 39 , 42 ].

In the muscle, weakness and proximal muscle wasting are induced by the catabolic effects of excess glucocorticoid on the skeletal muscle. Osteoporosis is caused by decreased intestinal and renal calcium absorption and increased bone resorption [ 43 ].

Localized scleroderma morphea and lupus erythematosus panniculitis lupus erythematosus profundus LEP are well-known connective tissue disorders involving the subcutaneous compartment resulting in lipoatrophy [ 44 ]. They are usually localized but rarely progress to acquired generalized lipoatrophy [ 12 ].

Morphea usually manifests as a single well-circumscribed lesion on the extremities or upper trunk, near the spine with keloid-like hard and shiny skin changes [ 45 ]. MRI shows localized lipoatrophy under the depressed thickened skin with or without varying degree of signal change in underlying fascia and musculature involvement.

It is usually asymptomatic and not associated with visceral involvement. Generalized morphea is the most severe form of localized morphea. A year-old woman with deep morphea on her right thigh.

a Axial fat saturated T2-weighted image shows hypersignal intensity in full thickness of subcutaneous fat on the anterior aspect arrow.

Increased signal intensity in gastrocnemius muscle asterisks , muscle fasciae, and diffuse subcutaneous septal thickening are also demonstrated. b T1-weighted image clearly shows thinning of subcutaneous fat with cord-like low signal intensity small arrows.

Linear scleroderma is characterized by one or more linear streaks of cutaneous induration that may involve the dermis, subcutaneous tissue, muscle, and underlying bone. Parry-Romberg syndrome PRS , also known as progressive hemifacial atrophy, clinically overlaps with LScs and can even affect the brain [ 47 ].

CT and MRI may show cerebral hemiatrophy or high signal of white matter on T2-weighted image ipsilateral to the affected facial side not only atrophy of the skin and underlying bone and soft tissue Fig.

A year-old man with Parry-Romberg syndrome. a Axial CT images show asymmetrically decreased subcutaneous fat on the left side arrows. b Hypoplasty of the left orbit is also evident. c Volume-rendered three-dimensional reformation image of facial bones highlights bony asymmetry of the face.

There is a perceivable asymmetry of the maxillary bone as well. d Coronal FLAIR image shows subcortical high signal intensity area arrowhead. LEP primarily involves subcutaneous tissues and tends to have a chronic course resulting in broad lipoatrophy. Face and limbs are most commonly involved [ 50 ].

Posttraumatic subcutaneous lipoatrophy occurs following a fall, blunt injury Fig. Often, the interval between the injury and initial observation of the deformity is prolonged. It is more prevalent in women and children, usually appearing on the shins, thighs, arms, breasts, and buttocks [ 52 ].

The radiologic appearance of subcutaneous posttraumatic lipoatrophy may accompany linear spiculated lesion with globular component on MRI, correlated with lipogranuloma pathologically [ 53 , 54 ].

A year-old woman with post blunt trauma lipoatrophy on the right upper arm. a Axial T2-weighted and b STIR images show thinning of subcutaneous fat on the lateral aspects arrows with multiple high signal nodules small arrows showing small peripheral fat signal areas.

c Photograph shows thinning of the lateral aspect of the upper arm with small hump arrow. d Histologically fat necrosis with lipogranuloma was proven.

Variably sized lipid vacuoles are surrounded by foam cells, foreign body-type arrows , and Touton giant cells arrowhead in the resected lipogranuloma.

A year-old woman with post-surgery lipoatrophy. a CT image before operation shows calcified soft tissue density mass anterior to the right kidney arrow. Right nephrectomy was done, and the lesion was pathologically diagnosed as dedifferentiated liposarcoma.

b CT image one month after surgery shows fluffy opacity in the subcutaneous fat around the operated area arrowhead with abdominal wall muscle swelling. Repetitive mechanical stress also induces a prominent increase in the volume of subcutaneous adipose tissue.

By carrying heavy loads, abnormal local fat accumulation on the shoulder has been reported in festival participants in Japan and Southern Italy, wine porters, brewery workers, and heavy handbag carriers [ 56 ].

On CT and MRI, an increase in the volume of non-capsulated adipose tissue is evident Fig. A year-old man with post-traumatic pseudolipoma on the right posterior neck. He had a history of carrying a mikoshi Japanese portable shrine daily.

a Axial T1-weighted and b sagittal post-contrast fat-sat T1-weighted images show non-capsulated subcutaneous fat tissue proliferation on the right posterior neck arrows. c Photograph of a mikoshi. The most widely accepted cause is repetitive microtrauma against such as the edge of furniture or tight-fitting clothes [ 57 ].

Other risk factors are reported to include overweight, routine electrical shock, clothing made of fibers, wearing of rubber-soled shoes, and low humidity air conditioning [ 58 ]. MRI shows a clear superficial loss of subcutaneous tissue without findings of panniculitis and thickening of interlobular septa with a reduction in the size of fat lobules [ 60 ].

A year-old woman with semicircular lipoatrophy. She had a history of working leaning against the edge of her desk daily. c , d Coronal localizer image and STIR show loss of localized subcutaneous fat tissue with slight edematous change circle.

Familial partial lipodystrophy is inherited in an autosomal dominant or recessive fashion showing a mixture of partial fat atrophy and accumulation with onset during childhood or puberty [ 12 ]. The phenotypic heterogeneity of familial partial lipodystrophy has been reported as types 1—6.

Lipoatrophy appears in childhood or early adolescence. In addition to lipodystrophy, this condition shows craniofacial and skeletal abnormalities including mandibular and clavicular hypoplasia, delayed closure of the cranial sutures, acro-osteolysis, joint contractures or bird-like facies with postnatal growth retardation, and cutaneous changes [ 12 ].

Approximately cases of acquired partial lipodystrophy have been reported. It typically shows a childhood or adolescent onset with a unique, cephalocaudal progression of fat loss with fat accumulation in the lower half of the body [ 63 ]. Infections, autoimmune diseases, and membranoproliferative glomerulonephritis have been linked to the development of acquired partial lipodystrophy [ 12 ].

Adipocytic tumors are the most common soft tissue tumors clinically, and radiologists always need to differentiate them from those conditions showing localized abnormal fat distribution discussed above.

Those atypical lipomas can resemble non-neoplastic abnormal fat distribution conditions. Lipomas are usually asymptomatic, though local pain, tenderness, or nerve compression is reported when they become large [ 65 ].

Abnormal non-neoplastic fat distribution conditions usually show no such symptoms though mechanical obstruction or metabolic dysfunction may also be present. Fat necrosis within a lipoma presents a variable imaging appearance with inflammatory or fibrotic change, and these can be difficult to differentiate from fat accumulation due to mechanical pressure or trauma, other benign adipose tumors, or well-differentiated liposarcoma.

Superficial lipoma in a year-old woman on the right shoulder. a T1-weighted image and b fat-suppressed T2-weighted show a homogeneous fatty mass arrows with a similar signal intensity to that of the adjacent subcutaneous fat but with a thin capsule and thin internal septa.

Angiolipoma is a benign neoplasm consisted of mature adipose tissue and vascular structures. It represents as well-defined multiple, small subcutaneous mass with tenderness located commonly in the forearm, upper arm, or trunk [ 66 ].

The MR imaging features of these lesions are the presence of fat nodules with or without low signal on T1- or T2-weighted images with or without high signal on fat saturated T2-weighted images representing the prominent vasculature [ 67 ] Fig. Angiolipoma in a year-old man on the left upper arm.

a T1-weighted image shows a subcutaneous tiny mass with inhomogeneous high to intermediate signal intensity arrow. b Fat-saturated T2-weighted image shows hyperintense signal with focal fat suppression arrowhead in the mass with connection to dilated subcutaneous vein small arrow. Non-adipose components are similar to those of skeletal muscle on T1-weighted imaging and hyperintense on fat-saturated fluid-sensitive sequences Fig.

The mass is generally firmer than lipomas or most conditions with non-neoplastic localized abnormal fat distribution. When it occurs in atypical locations, it becomes challenging to differentiate from liposarcomas or even other non-adipose soft tissue tumors.

Spindle cell lipoma in a year-old man with a painless mass on the posterior neck. a Axial T1-weighted image and b sagittal STIR image show a subcutaneous, encapsulated fatty mass arrows with amorphous non-fatty signal area arrowheads representing intermingled components such as collagen fibers, myxoid matrix, and vascular elements.

Lipomatosis of a nerve is a rare, not fully understood benign condition, which has been referred to variously as fibrolipomatous hamartoma, perineural lipoma, fatty infiltration of the nerve, or neural fibrolipoma [ 64 ].

Accompanying varying degrees of mesenchymal overgrowth including adipose tissue with frequent sensory symptoms such as paresthesia or numbness, with or without macrodactyly, is the typical presentation [ 71 ] Fig.

The location and adipose tissue distribution interspersing nerve bundles are imaging findings distinctive from those of already discussed non-neoplastic abnormal fat distribution conditions.

Lipomatosis of the median nerve in an year-old girl without symptoms. a Axial T2- and b coronal T1-weighted images reveal soft-tissue hypertrophy with predominance of fat in the radial side of the middle finger along with the neurovascular structure arrows.

It most commonly locates in a deep-seated well-vascularized area and rarely in subcutaneous locations [ 72 ]. Well-differentiated liposarcoma and ALT are synonyms describing similar lesions morphologically and karyotypically and are differentiated by the location of the tumor and the surgical resectability [ 66 ].

The term of well-differentiated liposarcoma is used for lesions exclusively in the retroperitoneum, mediastinum, and spermatic cord, while ALT is used for lesions arising elsewhere [ 66 ]. The imaging findings typically depict a fatty mass with thick and irregular septa, septal enhancement, and non-adipose areas with prominent mass effect, local encasement of vital organs, and asymmetrical distribution compared with those non-neoplastic conditions [ 73 ] Fig.

Atypical lipomatous tumor in a year-old male with a painless, firm, and mobile mass gradually increasing in the right back. a Coronal CT image shows a fat-containing inhomogeneous density mass arrow. b On post-contrast fat-saturated T1-weighted image, the non-fatty lesion shows moderate enhancement arrowheads.

Surgically diagnosed as ALT with abundant fat necrosis. Radiologists should be aware of the typical imaging findings and disease spectrum of abnormal deposition of subcutaneous fat.

Although the underlying conditions are diverse, the radiological findings can be the key making possible an early assessment and suggesting the optimal methods needed to achieve a definitive diagnosis.

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Ogino J, Saga K, Tamagawa M, Akutsu Y Magnetic resonance imaging of semicircular lipoatrophy. However, an individual with excessive visceral adipose tissue will continually send large amounts of fat to the liver, leading to fat accumulation in the liver cells ectopic fat and the development of non-alcoholic fatty liver disease.

This provokes inflammation and resistance to the effects of insulin, a hormone important in fat and sugar storage and metabolism.

In the long term, fatty liver can lead to serious alterations of liver function. The excess fat in the body also leads to fat being stored in the muscles. This affects muscle function and makes muscle more resistant to the action of insulin. Subcutaneous fat, on the other hand, not only releases its stored fats more slowly, but those fats enter the general circulation and reach the liver in lower concentrations, so they are less likely to cause damage.

The fat cells in visceral adipose tissue are different from those in subcutaneous fat. When fat stores increase, the adipose tissue can accommodate the extra fat by increasing the number of fat cells or by increasing their size. Both of these mechanisms are observed but, for various reasons, in visceral adipose tissue fewer new adipocytes fat cells appear than in subcutaneous adipose tissue, and there is a much greater increase in cell size.

Increased cell size provokes inflammation see my article on lipoinflammation here. This inflammation is considered to be the link between excess body fat and chronic diseases, such as heart disease, type 2 diabetes and cancer. See my article on chronic diseases associated with excess body fat here.

Oestrogens have been shown to promote fat accumulation in the gluteofemoral subcutaneous fat stores buttocks and thighs. Fat starts to accumulate in this region as girls reach puberty, and it typically persists until the menopause. After the menopause, oestrogen levels fall and the fat distribution in postmenopausal women changes to become similar to that seen in men.

Testosterone has been shown to increase lipid utilisation and decrease storage; this is part of the explanation why men typically have a lower body fat percentage than women.

In males, testosterone levels start to rise significantly during puberty and then fall progressively after years of age. As testosterone falls, men become more prone to accumulate body fat.

The reason why men tend to accumulate belly fat remains unclear. Genetic control and heritability. Body mass index has been shown to be influenced by genetic factors. Certain genes are directly involved in the control of body weight; for example, absence of the leptin gene leads to massive weight gain.

Studies of the human genome have identified around genetic variants that affect body weight and body fat distribution. Epigenetics is the way the environment alters expression of our genes.

Factors such as stress, inflammation and diet can alter gene expression, and this can change how we store or use fats and sugars. Even maternal factors before we are born can provoke epigenetic effects that will influence our body weight positively or negatively later in life.

Traditionally, body fat has been assessed using anthropometric measurements, such as waist and hip circumferences, weight, height and skinfold thicknesses, and then applying formulae to estimate body fat mass and distribution.

The waist-to-hip ratio WHR gives us a good idea of the gynoid or android fat distribution. The waist-to-height ratio WHtR gives us a good idea of the relative accumulation of abdominal fat made up of subcutaneous abdominal fat and visceral adipose tissue.

Technological advances have now given us devices that can determine body fat percentage and distribution accurately: DEXA, BodPod, bioelectrical impedance analysis bioimpedance see my articles on body fat percentage and bioimpedance. While DEXA and the Bod Pod are more expensive and less widely available, bioimpedance devices are now used in many weight management clinics and are often available in gyms and health clubs.

Health professionals must be fully aware of the effects of excess fat on health and how the distribution of that fat can change the relative risks. We need to be able to assess fat mass and its distribution accurately and to interpret the findings according to patient age, sex and ethnicity.

Excess visceral adipose tissue is the fat most closely linked to ectopic fat deposition and chronic disease; the sooner it is eliminated the better. Its presence therefore demands more intensive, active weight loss measures.

It must be recognised that fat on the hips and thighs can be more difficult to move and requires approaches that act at a cellular level to increase the breakdown of triglycerides and the release of fat for energy utilisation. The choice of diet programme and the type of exercise regimen will play a major role in this process.

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