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. Author manuscript; available in PMC: 2020 Sep 1.
Published in final edited form as: Curr Obes Rep. 2019 Sep;8(3):243–254. doi: 10.1007/s13679-019-00349-x

Ethnic Disparities in Adiposity: Focus on Nonalcoholic Fatty Liver Disease, Visceral, and Generalized Obesity

Uchenna Agbim 1, Rotonya M Carr 2, Octavia Pickett-Blakely 2, Sam Dagogo-Jack 3
PMCID: PMC6662200  NIHMSID: NIHMS1530471  PMID: 31144261

Abstract

Purpose of review:

Excessive adiposity has become a public health problem worldwide, contributing to the rise in obesity-related diseases and associated morbidity and mortality. This review details the relative significance of race/ethnicity as it pertains to adiposity and non-alcoholic fatty liver disease (NAFLD).

Recent Findings:

Fat distribution remains a more reliable measure of adiposity than anthropometric measures, with visceral adipose tissue (VAT) associated with increased risk of cardiometabolic disease. While obesity is the most common risk factor for NAFLD, the racial/ethnic prevalence of obesity does not completely parallel NAFLD risk.

Summary:

Combating racial/ethnic disparities in obesity requires understanding differential risk among various groups. Hispanics are disproportionally impacted by NAFLD and have high rates of obesity, VAT, and insulin resistance (IR). This contrasts with Blacks, who have high prevalence of obesity and IR, accompanied by a paradoxically favorable lipid profile and low prevalence of VAT and NAFLD. Many features of adiposity and NAFLD are mediated by genetic and environmental factors, the latter being modifiable and the focus of interventions.

Introduction

The rise in global prevalence of obesity and comorbid conditions such as type 2 diabetes mellitus (T2DM), metabolic syndrome, non-alcoholic fatty liver disease (NAFLD), cardiovascular disease, and kidney disease is well-described in the literature. Perhaps counterintuitively, excessive adiposity alone does not predict risk of these obesity-related metabolic consequences. Rather, the distribution of fat is a more important determinant of these metabolic diseases. Thus, obesity is a heterogeneous condition that has varying manifestations regarding co-morbidities. Population-based data show racial/ethnic differences in the prevalence of obesity and related conditions. For example, in the U.S., ethnic minorities have a disproportionate burden of these conditions compared to their white counterparts due to complex genetic, socioeconomic, and behavioral factors. While the general NAFLD prevalence parallels that of obesity, the prevalence of NAFLD in racial/ethnic groups does not appear to follow suit. In the present review, we discuss racial/ethnic differences in adiposity with particular attention to generalized adiposity, visceral adiposity, and NAFLD.

Epidemiology of Adiposity and NAFLD

Historically, the underweight population was approximately twice that of the obesity population; however, current data indicate that more people worldwide suffer from obesity than underweight [1]. The global prevalence of overweight, as defined by a body mass index (BMI) of ≥25 kg/m2, is 36.9% in men and 38% in women, respectively [2], and that of obesity (BMI ≥30 kg/m2) is 10.8% in men and 14.9% in women, respectively [2]. The adult prevalence of obesity adults in the United States is 39.6%, based on the National Health and Nutrition Examination Survey (NHANES) from 2015–2016; the same survey reported 18.5% obesity prevalence in children/youth. Obesity accounts for 72% of the rise in diabetes [3], and is also a well-known independent risk factor for cardiovascular disease, hypertension, stroke, obstructive sleep apnea, chronic kidney disease, among myriad co-morbidities [4].

Similarly, obesity is a major risk factor for non-alcoholic fatty liver disease (NAFLD), a disease characterized by >5% fat accumulation in the liver, in the absence of other etiologies of hepatic steatosis. The inflammatory component of NAFLD, termed non-alcoholic steatohepatitis (NASH), may lead to chronic fibrosis, cirrhosis, portal hypertension and even hepatocellular carcinoma. Estimates reveal the global NAFLD prevalence is 25.2% and NASH prevalence among those with NAFLD is 59.1% [5].

Pathophysiology of NAFLD and Variations in Adiposity Distribution

Insulin resistance (IR) is a cardinal feature of both excess adiposity and NAFLD [6]. Adipose tissue (AT) serves a dual role as a fat storage depot and an endocrine organ. In the setting of increased adiposity, adipocytes release free fatty acids (FFA) and cytokines that impair insulin signaling and increase peripheral tissue inflammation. Ultimately, FFA are deposited at ectopic depots (skeletal muscle, liver, pancreas, etc.), where they eventually exhaust the storage and oxidative capacity of these organs and are transformed into toxic compounds [7]. The IR triggers compensatory hyperinsulinemia, which stimulated de novo hepatic lipogenesis, further exacerbating NAFLD [8]. Indeed, IR has been linked to obesity-related disorders, including cardiovascular disease, T2DM, and cerebrovascular disease [7].

Fat patterning refers to the regional location or distribution of AT deposition. Subcutaneous AT (SAT) is stored in the subcutaneous area, representing the majority of AT, while visceral AT (VAT) occurs in the viscera, contributing to a wide variety of metabolic dysfunction including IR, T2DM, dyslipidemia, and inflammation [9, 10]. One hypothesis suggests VAT is a marker of excess adiposity, whereby SAT’s ability to expand, or serve as a metabolic sink, becomes limited, shifting fat from SAT to VAT and other ectopic depots [9]. Other literature supports the concept of VAT as a metabolically active depot that releases vasooactive substances and adipocytokines into the portal circulation [10].

Interestingly, evidence from the Framingham Heart Study (FHS) [10] and Jackson Heart Study (JHS) [11] showed significant associations between cardiometabolic risk and SAT, VAT and NAFLD. However, VAT had a stronger association with cardiometabolic risk than SAT or NAFLD [10, 11]. Furthermore, VAT is a stronger etiologic determinant of NAFLD than general adiposity [12, 13]. Specifically, VAT is intimately involved in inflammation and fibrosis in a dose-dependent fashion, independent of hepatic steatosis and metabolic risk factors. Thus, it is VAT, rather than SAT, which propels an atherogenic, diabetogenic milieu and NAFLD. SAT may serve as a favorable protective function, given its association with decreased triglycerides and increased high-density lipoprotein (HDL) [13]. In fact, the International Diabetes Federation (IDF) issued a statement characterizing VAT as the foundation of the metabolic syndrome [14].

Gluteofemoral AT (GAT) and pericardial fat have variable association with cardiometabolic disease. In general, GAT has a protective effect on obesity-related diseases. Like VAT, pericardial fat depots contribute to cardiovascular disease via IR and local release of adipocytokines within the heart [15, 16].

2) Anthropometric and Imaging Measures of Adiposity

There continues to be controversy regarding the most appropriate metric of obesity. Ideally, such a measure should not only correlate with body fat proportion (BF%) but also integrate the pathological consequences of fat mass [9] and should be valid without regard to sex, age, or race [17]. BMI is considered a crude marker of adiposity as it cannot distinguish lean body mass from fat mass, fails to characterize fat distribution, and varies by sex despite comparable BF% [7, 18]. BMI also overestimates adiposity in populations of African descent, who have higher bone density and muscle mass compared with other groups. Other metrics include waist-to-hip ratio, waist-to-height ratio, waist circumference (WC) and even neck circumference [4, 10, 14, 19, 20]. Imaging techniques include dual energy X-ray absorptiometry, computerized tomography, and magnetic resonance imaging (MRI) [9, 21, 19].

Metabolically Healthy Obese and Lean Phenotypes

An appreciation of heterogeneity in the expression of metabolic risks associated with obesity has spawned notions of metabolically healthy and metabolically unhealthy obese and lean phenotypes. The term metabolically healthy obese (MHO) characterizes subjects who are obese by BMI, but do not possess the typical metabolic impairments associated with obesity [22]. Some believe MHO may be a transient phenotype that shifts to metabolically unhealthy obese (MUO) over time [22]. The MHO phenotype is generally associated with preserved insulin sensitivity and low risk for development of NAFLD [23]. However, NAFLD does occurs over time in obese people as AT becomes more resistant. This may explain the findings of a South Korean study, where MHO men and women (without baseline fatty liver disease) developed incident NAFLD over time, thereby becoming MUO [24]. Similarly, another study from Asia noted that the transition from MHO to MUO was independently associated with VAT [25]. Nevertheless, the MHO individuals may be at risk for adverse cardiovascular events: in a study of 3.5 million individuals without the metabolic risk factors of dyslipidemia, hypertension, or T2DM, those with MHO had a 49% increased risk of coronary artery disease, 7% increased risk of cerebrovascular disease, and 96% increased risk of heart failure compared to those of normal weight without the aforementioned risk factors [26]. The prevalence of MHO among the overall NAFLD population is approximately 3–30% [2729]. While subjects with lean NAFLD may have normal weight, they have a body profile characterized by increased VAT and IR. Lean NAFLD habitus is associated with genetic polymorphisms in the patatin-like phospholipase domain containing 3 (PNLPA3) [28, 29], transmembrane 6 superfamily 2 (TM6SF2), sterol regulatory element-binding factor 2 (SREBF-2), or cholesteryl ester transfer protein (CETP) [29]. Interestingly, a retrospective cohort study in Sweden spanning 19.9 years of 646 biopsy-proven NAFLD subjects noted that while patients with lean NAFLD had better, albeit abnormal metabolic profiles at baseline compared to overweight subjects with NAFLD, the lean NAFLD patients had a two-fold increase in liver-related mortality, while those with obesity had no increased risk in liver-related mortality even after adjusting for age, sex, T2DM, and fibrosis stage. Thus, the authors suggest NAFLD may be accelerated in lean NAFLD subjects [27].

A recent longitudinal study compared metabolic profile and incident prediabetes during five years of follow-up among initially normoglycemic adults stratified by insulin-sensitive and insulin-resistant obese and lean phenotypes. The findings showed insulin-sensitive obese subjects had lower VAT, higher adiponectin levels, and a lower risk of incident prediabetes compared with insulin-resistant obese subjects [30]. Remarkably, in the same study, insulin-resistant lean subjects had higher VAT, lower serum adiponectin levels and an 80% higher risk of progression to prediabetes compared with their insulin-sensitive lean counterparts. Thus, acceleration of NAFLD [27] as well as dysglycemia occurs in lean subjects with IR [30].

Genetic versus Environmental Susceptibility to Adiposity

Varying theories exist regarding the ontogeny of obesity. The “thrifty genotype” surmises the ability of hunter-gatherer societies to conserve energy by storing fat in period of food abundance and utilizing this (“thrifty gene”) in periods of famine became less favorable with the transition to a more developed society [31]. With mounting information regarding diabetes development, this hypothesis was revised, acknowledging diabetes, obesity, and hypertension are multifaceted conditions with genetic and complex environmental pressures [32]. Conversely, the “drifty genes” theory discounts positive selection’s role, instead attributing obesity to variations in genetic frequency or “drift”, which powerfully emerged and persisted in times of food abundance [33]. The latter genetic theory remains more plausible, particularly in the setting of dietary overindulgence. Nevertheless, robust evidence implicates genetic variants associated with the accumulation of VAT [34], GAT or SAT [35], and the development of NAFLD [8, 34, 3640].

While genetics play a part in excess body weight, the environment’s role cannot be overlooked, as attributes of social networks, individual preferences, and socioeconomic status influence obesity. Using spatial and temporal analytic methods, BMI has been shown to vary depending on cumulative exposure to neighborhood poverty and co-ethnic density. For instance, cumulative poverty exposure was more predictive of BMI in non-Hispanic whites (NHW) than current poverty level [41]. Additionally, NHANES data demonstrate the obesity prevalence increases with decreasing urbanization [42]. Furthermore, data from the United States Centers for Disease Control and Prevention show an inverse association between obesity prevalence and higher socioeconomic status (as indicated by education and income) [43]. The studies support complex but potentially modifiable interaction between social determinants of health and obesity risk, an area that deserves further scrutiny.

Racial/Ethnic Disparities in Generalized Obesity

Data from the FHS, (a predominantly NHW population) and JHS [a predominantly non-Hispanic black (NHB) population] reveal higher rates of obesity among NHBs compared to NHWs [44]. Similarly, data from NHANES show that age-adjusted prevalence of obesity in adults ≥20 years is highest among Hispanics (47.0%) and NHBs (46.8%) compared to NHWs (37.9%) and Asians (12.7%). The same trend follows in children and youth, with Hispanics having the highest obesity prevalence at 25.8% and Asians having the lowest obesity prevalence at 11% [45]. Table 1 shows racial/ethnic comparisons in adiposity and NAFLD. By gender, NHB women have the highest obesity prevalence, followed by Hispanic women, and NHW women. Among men, Hispanics have the highest obesity prevalence, followed by NHW and NHB [45]. While sex hormones account for differences across sex, with androgens associated with decreased adiposity, sex hormones do not explain differences in adiposity across race/ethnicity [46]. Plasma levels of adiponectin, an adipocytokine associated with improved cardiometabolic health, display gender and ethnic disparities: levels are higher in NHWs compared to NHBs, and in women compared to men [47].

Table 1.

Measures of Adiposity and NAFLD in Studies of Various Racial and Ethnic Groups

Population Metric NHW NHB Hispanic Asian
Total Men Women Total Men Women Total Men Women Total Men Women
NHANES Adults [1] BMI≥30kg/m2 Prevalence, % 37.9 37.9 38.0 46.8 36.9 54.8 47.0 43.1 50.6 12.7 10.1 14.8
California [2] BMI≥30kg/m2 Prevalence, % 21.1 33.3 28.8 9.0
NHANES adolescents[3] BF% across all BMIs 24.3 34.0 21.8 33.6 25.6a 35.9a
New York City [4] BF%atBMIof25 kg/m2 19.2 34.2 23.6 36.8
California [5] BMI, kg/m2 26.5 27.9 28.1 23.9
DHS [6] Visceral Body Fat, % 7.4 3.8 6.8 3.4 8.3 4.4
Overweight and obese youth in an obesity clinic [7] Visceral Body Fat, cm3 75.1 67.4 66.4
DHS [8] Prevalence of NAFLD by 1H-MRS, % 33 42 24 24 23 24 45 45 45
NASH CRN [9] Prevalence of NASH among biopsy-proven NAFLD, % 62 52 63 52
Overweight and obese youth in an obesity Clinic [7] Prevalence of NAFLD by MRI,% 42.9 15.7 59.6
a

Mexican American; BF%: Body fat percentage; BMI: Body mass index; 1H-MRS: Proton magnetic resonance spectroscopy; DHS: Dallas Heart Study IDF: International Diabetes Federation; MRI: magnetic resonance imaging; NAFLD: Non-alcoholic fatty liver disease; NASH: NASH Nonalcoholic steatohepatitis; NASH CRN: Nonalcoholic Steatohepatitis Clinical Research Network; NHANES: National Health and Nutrition Examination Survey; NHB: Non-Hispanic black; NHW: Non-Hispanic white

The comparative impact of BMI as a marker of co-morbidities across ethnic groups has been a focus of research. Wong et al. [48] demonstrated that for each 1-unit increase in BMI, Asians had higher risk of hypertension and diabetes compared to NHWs, Hispanics, and NHBs, indicating incremental weight gain in Asians is more detrimental. A study using NHANES data found that BMI-concordant Mexican-American, NHW, and NHB adolescents had divergent adiposity (BF%): Mexican American adolescents had higher BF% and NHB adolescents had lower BF%, at the same BMI [19].

Furthermore, other anthropometric measures (e.g., WC, waist-to-height ratio, waist-to-hip ratio) have differential impact on mortality across racial/ethnic groups, as shown in a longitudinal study of NHWs and NHBs in Louisiana [20]. Katzmartzyk et al. [20] followed a cohort, linking baseline clinical and demographic data to death records, and determined that the aforementioned anthropometric measures associated with adjusted all-cause mortality in NHWs but not in NHBs, despite a higher absolute death rate among the latter. It is known that among individuals with the MHO phenotype, NHBs tend to spend a longer duration of time in the MHO state before transitioning to MUO state compared to NHWs [22].

Experts have long advocated the adoption of race/ethnic-specific BMI parameters, particularly among Asians [17, 4951], who have higher BF% at lower BMI compared with than NHWs [17, 49]. The World Health Organization proposes BMI cut-offs of 23 kg/m2, 27.5 kg/m2, 32.5 kg/m2, and 37.5 kg/m2 for risk stratification in Asian populations. Accordingly, a BMI range from 18–23 kg/m2 denotes acceptable borderline risk of cardiovascular and obesity-related diseases, 23–27.5 kg/m2 denotes increased risk, and ≥27.5 kg/m2 indicates high risk. These ranges acknowledge the heterogeneity within the Asian population, as BF% differs among Asian subgroups, and allow countries to determine the exact cut-off value in each range [52]. Comparably, the American Diabetes Association has proposed screening Asian American adults with a BMI ≥23 kg/m2 for diabetes [53]. Much of the literature on obesity standards were developed with white ancestry as the reference group, which limits generalizability to other populations [17, 54].

Racial/Ethnic Disparities in Visceral Adiposity and Other Ectopic Depots

There are known differences in fat distribution across racial/ethnic groups. When total body fat is controlled, persons of South Asian and Chinese ancestry have more VAT than Europeans and obesity tends to be underestimated in the former groups [55]. Furthermore, it is established that NHBs have lower VAT compared to NHWs and Hispanics, after adjusting for pertinent variables [12, 44, 54, 56]. There are also data that NHWs accumulate VAT to a greater extent than NHBs during dynamic change in adiposity [56]. Findings from the Framingham and Jackson Heart studies provide insight into the differential contribution of VAT to cardiovascular morbidity in NHB and NHW women, with VAT exerting a less toxic effect among NHB women [44]. Thus, an obesity paradox has been described with the observation that NHBs possess less of the noxious VAT, lower triglycerides and higher HDL cholesterol levels but have higher prevalence of hypertension and T2DM [16, 44, 56].

Other fat depots also differ according to race/ethnicity and sex. For instance, NHB men have more abdominal SAT [12, 56] compared to NHWs and Hispanics, and increased lower extremity fat compared to Hispanics [12]. NHB women have similar amount of SAT compared to Hispanics [12], but more compared to NHWs [12, 56]. Pericardial adipose tissue (PAT) and calcification were assessed with cardiac CT in the Multi-Ethnic Study of Atherosclerosis [57]. NHBs had the lowest PAT compared with Hispanics, Asians and NHWs.

Racial/Ethnic Disparities in NAFLD and NASH

Evidence from Clinical Studies

There is significant racial/ethnic variability in the prevalence and characteristics of NAFLD. Data from the Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN) revealed that 61% of patients with biopsy-proven NAFLD had NASH; the frequency of NASH by race/ethnicity was 63% in Hispanics, 62% in NHWs, 52% in NHBs, and 52% in Asians [58]. Blacks and Asians have lower burden of NASH than Hispanics and NHWs. Additionally, in a study of 226 NHWs and NHBs with BMI ≥35 kg/m2 undergoing bariatric surgery, Browning and colleagues found that NHWs were three times more likely to have NAFLD and four times more likely to have NASH than NHBs [59]. When the groups were stratified by T2DM status, NHWs were still more likely to have both NAFLD and NASH [59]. Among overweight and obese youth studied longitudinally, NAFLD occurred less frequently among black youth compared with Hispanics and NHWs [8]. However, black youth who developed NAFLD had more severe metabolic comorbidities, including prediabetes and T2DM, than white and Hispanic youth [8].

Microscopic and Advanced Imaging Studies

Histologic studies of liver biopsies showed that NHBs had less inflammation, Asians had more severe ballooning, and Hispanics had more Mallory bodies, compared to NHWs [60]. However, no racial/ethnic differences have been reported for fibrosis [60, 61], a major determinant of outcomes among NAFLD patients [62]. Using proton magnetic resonance spectroscopy, which identifies triglyceride content [21], Browning et al. [63] reported that NAFLD prevalence in the Dallas Heart Study population was highest among Hispanics (45%) and lowest among NHBs (24%), and intermediate among NHWs (33%). The authors propose that the decreased prevalence of NAFLD in NHBs, despite high obesity and IR, may be due to differences in lipid homeostasis [63]. Indeed, NHBs appear to enjoy relative protection from the development of NAFLD, despite high prevalence of obesity and IR. As observed in the general population, reports abound on the lower triglycerides and higher HDL cholesterol levels of NHBs, compared with other groups in the NAFLD literature [12, 58, 60, 63]. Moreover, in a study of 70 NHB and NHW women with BMI ≥40 kg/m2, NHB women with biopsy-proven simple steatosis had a more favorable lipoprotein profile compared to NHW women, even when the NHB women were more obese and insulin resistant. Remarkably, no NHB women in the study showed evidence of NASH, whereas 41% of the NHWs did so [64].

Role of Insulin Resistance and VAT

As hepatic steatosis is strongly related to VAT, ethnic differences in VAT may explain variability in NAFLD. A study examining fatty liver among 57 obese NHB and NHW male youth in the United States demonstrated that VAT was the only factor associated with having fatty liver independent of age, ethnicity, total body fat, fat-free mass, abdominal SAT, and cardiorespiratory fitness [65]. In contrast, SAT and lower extremity fat were not associated with hepatic triglyceride content [12]. After controlling for percentage of VAT, levels of hepatic triglyceride content were comparable among ethnic groups. The same trend did not persist after controlling for typical metabolic risk factors such as IR, total adiposity, or other fat depots. The authors postulate that their findings may be explained by differential manifestations of IR across racial/ethnic groups. Despite having greater IR than NHWs, NHBs have lower triglyceride levels, and are less likely to deposit fat in the viscera with increasing adiposity, compared to NHWs and other groups [12]. IR conferred increased risk for NASH among NHWs, but not among Hispanics in the NASH CRN cohort [58]. Coupled with findings from the Dallas Heart Study, showing decreased prevalence of NAFLD among NHBs despite high IR [63], the latter suggests that the intersection of IR and metabolic abnormalities on NAFLD has variable impacts among the different racial/ethnic groups.

Data from Matched Studies

One of the limitations of the Dallas Heart Study and other studies [60, 63] is the absence of a matched control group, to rigorously assess the ethnic data. In this regard, Lomonaco et al. [66] carefully matched Hispanics to NHWs based on age, sex, BMI or body fat and found no significant difference in NASH prevalence. When looking at the histological features of biopsy-proven NASH, no significant differences were found in the specific NASH components (steatosis, ballooning necrosis, lobular inflammation) in Hispanics compared to NHWs. Furthermore, upon examining validated measures of hepatic insulin sensitivity, AT insulin sensitivity, and muscle insulin sensitivity, there were no significant differences between NHWs with NASH and Hispanics with NASH. The data showed that patients with NASH, regardless of ethnicity, had IR at the level of hepatic, adipose, and muscle tissue compared to those without NASH. The only significant ethnic difference in the study by Lomonaco et al. [66] was a subgroup analysis of T2DM patients with NASH that showed more biopsy-proven fibrosis in Hispanics than NHWs. These findings suggest when all confounding factors are accounted for and controlled, there may be no significant ethnic differences in IR among Hispanics and whites with NASH [66].

Similarly, the idea that NHBs are protected from NAFLD has been challenged. However, a study of 67 NHB subjects propensity matched in a 2:1 fashion with white subjects (for age, sex, BMI, hemoglobin A1c, and T2DM) found that a greater proportion of the white subjects had NAFLD compared to black subjects (51.9% vs. 25.0%; P=0.003). No significant differences were observed in peripheral or adipose tissue IR. The black participants had lower total body fat, lower triglycerides, higher HDL cholesterol, and lower hepatic triglycerides, despite having similar BMI as white subjects [67]. In further analysis, when black and white participants were stratified according to NAFLD prevalence, there was no difference in amount of hepatic fat but the ethnic differences in triglyceride and HDL cholesterol persisted. Histological study of biopsies from participants with NAFLD showed no significant difference in the frequency (73.3% vs 57.1%; P = 0.12) or histological features of NASH between whites and black subjects [67]. Thus, once NHBs develop NAFLD, histological findings and disease severity are no different from those seen in NHWs. Although Blacks appear to have lower risk than other racial/ethnic groups, clinical vigilance for NAFLD should be maintained without exclusion, as Blacks with NAFLD have the same risk of NASH as other groups [67].

Genetic versus Environmental Factors in NAFLD

Gene Variants

Genome-wide association studies and family aggregation studies have identified specific polymorphisms associated with the risk of developing NAFLD [8, 34, 3639]. For example, the discovery of the SNP, PNPLA3 rs738409 variant, has advanced knowledge regarding the genetics of NASH. Using data from the Dallas Heart Study, Romeo et al. [34] demonstrated that the PNPLA3 rs738409 guanine (G) allele was significantly associated with hepatic triglyceride content in all ethnicities, but not traditional metabolic risk factors. Indeed, the frequency of the high-risk G allele paralleled the prevalence of NAFLD among Hispanics, NHWs, and NHBs [34]. These findings have been replicated in additional studies [8, 39], and additional gene variants with impact on race/ethnicity have been reported [36, 37]. The G allele of PNPLA3 rs738409 has been associated with increased risk of NAFLD in Chinese and Hong Kong Asians [68] as well as in non-obese or lean individuals [28]. NAFLD patients of lean stature may harbors polymorphisms in PNLPA3 [28, 29], TM6SF2, SREBF-2, or CETP [29]. Recently, a variant in 17-beta-hydroxysteroid dehydrogenase 13 (HSD17B13) has been associated with decreased risk of progression from steatosis to NASH in persons of Hispanic and European ancestry [40].

Environmental (Behavioral) Factors

Studies have identified certain behavioral risk factors among patients with NAFLD, including fast food consumption [69], infrequent physical activity [69, 70], and sedentariness [70]. Data from the NASH CRN reported increased carbohydrate consumption, less participation in physical activity, and lower income levels in Hispanics compared to NHWs with NASH [58]. These behavioral risk factors seem to characterize NAFLD globally. Figure 1 shows the prevalence of NAFLD juxtaposed with energy balance in kilocalories worldwide [71]. The highest prevalence is in South America and the lowest is in Africa; the overlap between NAFLD prevalence and energy balance is inexact. Thus, while the prevalence of NAFLD seems to increase with prevalence of obesity globally, there are variations that suggest important influences from genetics and environmental factors cannot be ignored [71]. Data from the Multi-Ethnic Study of Atherosclerosis (MESA) provides insight into the heterogeneity of NAFLD in Hispanics: Hispanics of Mexican ancestry had higher prevalence than those of Caribbean ancestry [72], which may reflect the African ancestry of Caribbean Hispanics. Retrospective data from Asian-Pacific countries show that the prevalence of biopsy-proven NAFLD ranges from 46.1%–97.4% depending on the country and population studied [73], again indicating marked heterogeneity among Asian.

Figure 1.

Figure 1.

Global Prevalence of NAFLD and concordance with calorie intake. Horizontal color squares represent energy balance in kilocalories. Reproduced from Rinella M, Charlton M. The globalization of nonalcoholic fatty liver disease: Prevalence and impact on world health. Hepatology (Baltimore, Md). 2016;64(1):19–22, with permission from John Wiley and Sons.

Therapeutic Interventions for Obesity and NAFLD

Broadly, lifestyle modifications via moderate-intensity physical activity and caloric restriction, pharmacotherapy, and surgery (restrictive or malabsorptive surgery) remain strategies to mitigate the detrimental effect of obesity. Table 2 summarizes some intervention studies that utilized lifestyle modification and various medications, principally, for induction of weight loss in obese subjects. As significant loss of body fat usually improves NAFLD, many of these interventions may have salutary effects in patients with NAFLD. All interventions cause more SAT loss than VAT loss, but percentage change in VAT is greater than that of SAT [74]. NHBs have lower energy expenditure than NHWs which may reflect the decreased weight loss for a given energy prescription, as seen in a study of NHB and NHW women during a weight loss lifestyle intervention [75, 76]. Each of the six Food and Drug Administration (FDA)-approved medications for treatment of obesity has an estimated efficacy of 3–7% net weight loss [77]. NHWs were more likely to have a greater percentage of excess weight loss than NHBs in a systematic review of outcomes after bariatric surgery [78], but this is not explained by demographic, clinical or behavioral factors [79]. In a multi-ethnic study of diabetic subjects undergoing bariatric surgery, NHBs and Asians were less likely to have a durable decrease in their metabolic profile with time, and Asians were less likely to continue to lose weight after six months compared to NHWs and Hispanics [80].

Table 2.

Therapeutic Strategies for Obesity and NAFLD

Approach Comments References
Lifestyle [70, 74, 77, 82]
Hypocaloric diet
Moderate intensity physical activity
Optimization of diabetes, hypertension, lipids
Pharmacotherapy [77, 82]
Liraglutide FDA approved for obesity
Lorcaserin FDA approved for obesity
Naltrexone/bupropion FDA approved for obesity
Orlistat FDA approved for obesity
Pioglitazone For use in biopsy-proven NASH in select populations- + diabetes
Phentermine FDA approved for obesity for short-term use
Phentermine/topiramate FDA approved for obesity
Vitamin E For use in biopsy-proven NASH in select populations- not diabetic or cirrhotic
Bariatric Surgery [74, 7880]
Roux-en-Y Gastric Bypass Malabsorptive
Laparoscopic Sleeve Gastrectomy Restrictive
Gastric banding Restrictive

NAFLD: Non-alcoholic fatty liver disease; NASH: Non-alcoholic steatohepatitis

Although several medications (e.g., thiazolidinediones, Vitamin E, recombinant human leptin, etc.) have been tested in clinical trials, there are no FDA-approved medications for the specific treatment of NAFLD. Thus, lifestyle modification remains the backbone of treatment, and can be helpful in adherent patients [74, 81]. In February 2019, it was announced that obeticholic acid, a farsenoid X receptor agonist that decreases hepatic gluconeogenesis, lipogenesis, and steatosis, met primary endpoint in a phase 3 study [82], but further research is needed before approval by FDA for clinical use. Currently there are no reported racial/ethnic differences in response to interventions for management of NASH.

Conclusions

In this review, we detailed the significant impact of obesity and obesity-related diseases on morbidity and discussed the pitfalls of various anthropometric measurements as surrogates for adiposity across ethnic groups. For instance, Asians tend to have more adiposity for a given BMI, which could be regarded as normal in other race/ethnicities. We underscored the importance of fat distribution, stressing the role of VAT as a powerful association of cardiometabolic disease but also noting racial/ethnic disparities in the prevalence of generalized obesity, VAT, and NAFLD. For example, it appears puzzling that NHBs have high rates of generalized obesity and T2DM but have low rates of VAT and NAFLD. Furthermore, we discussed how genetic and environmental factors contribute to adiposity and NAFLD, with specific genetic features implicated in NAFLD prevalence among Hispanics, but yet unclear contributions of recently discovered NAFLD polymorphisms like HSD17B3. Finally, we stressed the role of modifiable factors like healthy food choices, physical activity, and the allostatic load faced by racial/ethnic groups as priority areas for interventions to combat the obesity epidemic and associated NAFLD and cardiometabolic disorders [74, 77, 81].

Acknowledgments

Sam Dagogo-Jack has received research support through diabetes clinical trial contracts with the University of Tennessee unrelated to the content of this article from AstraZeneca and Boehringer Ingelheim, and has received consultant honoraria for diabetes scientific advisory boards unrelated to the content of this article from Merck, Sanofi, AstraZeneca, Boehringer Ingelhim, and Janssen.

Abbreviations

AT

Adipose tissue

BF%

Body fat percentage

BMI

Body mass index

DHS

Dallas Heart Study

FDA

Food and Drug Administration

FFA

Free fatty acids

FHS

Framingham Heart Study

GAT

Gluteofemoral adipose tissue

HDL

High-density lipoprotein

IDF

International Diabetes Federation

IR

Insulin resistance

JHS

Jackson Heart Study

MESA

Multi-Ethnic Study of Atherosclerosis

MHO

Metabolically healthy obese

MRI

Magnetic resonance imaging

MUO

Metabolically unhealthy obese

NAFLD

Non-alcoholic fatty liver disease

NASH

Non-alcoholic steatohepatitis

NASH CRN

Nonalcoholic Steatohepatitis Clinical Research Network NHANES: National Health and Nutrition Examination Survey

NHB

Non-Hispanic black

NHW

Non-Hispanic white

PNPLA3

Patatin-like phospholipase domain containing 3

SAT

Subcutaneous adipose tissue

SNP

Single nucleotide polymorphism

T2DM

Type 2 diabetes mellitus

VAT

Visceral adipose tissue

VLDL

Very low-density lipoprotein

WC

Waist circumference

Footnotes

Publisher's Disclaimer: This Author Accepted Manuscript is a PDF file of a an unedited peer-reviewed manuscript that has been accepted for publication but has not been copyedited or corrected. The official version of record that is published in the journal is kept up to date and so may therefore differ from this version.

Conflict of Interest

Uchenna Agbim declares that she has no conflict of interest.

Rotonya M. Carr has served as Co-Investigator on a study sponsored by Intercept Pharmaceuticals and has received salary support from Intercept Pharmaceuticals.

Octavia Pickett-Blakely declares that she has no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

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