Gender differences in the association of visceral and subcutaneous adiposity with adiponectin in African Americans: the Jackson Heart Study
TL;DR: The statistically significant inverse association of VAT and adiponectin persisted after additionally adjusting for SAT, body mass index (BMI) and waist circumference (WC), suggesting that VAT provides significant information above and beyond BMI and WC.
Abstract: Adiponectin, paradoxically reduced in obesity and with lower levels in African Americans (AA), modulates several cardiometabolic risk factors. Because abdominal visceral adipose tissue (VAT), known to be reduced in AA, and subcutaneous adipose tissue (SAT) compartments may confer differential metabolic risk profiles, we investigated the associations of VAT and SAT with serum adiponectin, separately by gender, with the hypothesis that VAT is more strongly inversely associated with adiponectin than SAT. Participants from the Jackson Heart Study, an ongoing cohort of AA (n = 2,799; 64% women; mean age, 55 ± 11 years) underwent computer tomography assessment of SAT and VAT volumes, and had stored serum specimens analyzed for adiponectin levels. These levels were examined by gender in relation to increments of VAT and SAT. Compared to women, men had significantly lower mean levels of adiponectin (3.9 ± 3.0 μg/mL vs. 6.0 ± 4.4 μg/mL; p < 0.01) and mean volume of SAT (1,721 ± 803 cm3 vs. 2,668 ± 968 cm3; p < 0.01) but significantly higher mean volume of VAT (884 ± 416 cm3 vs. 801 ± 363 cm3; p < 0.01). Among women, a one standard deviation increment in VAT was inversely associated with adiponectin (β = − 0.13; p < 0.0001) after controlling for age, systolic blood pressure, fasting plasma glucose, high-density lipoprotein cholesterol, triglycerides, education, pack-years of smoking and daily intake of alcohol. The statistically significant inverse association of VAT and adiponectin persisted after additionally adjusting for SAT, body mass index (BMI) and waist circumference (WC), suggesting that VAT provides significant information above and beyond BMI and WC. Among men, after the same multivariable adjustment, there was a direct association of SAT and adiponectin (β = 0.18; p = 0.002) that persisted when controlling for BMI and WC, supporting a beneficial effect of SAT. Insulin resistance mediated the association of SAT with adiponectin in women. In African Americans, abdominal visceral adipose tissue had an inverse association with serum adiponectin concentrations only among women. Abdominal subcutaneous adipose tissue appeared as a protective fat depot in men.
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TL;DR: The role of adipocytokines and proinflammatory cytokines in the pathogenesis of NAFLD is explored, particularly on adiponectin, leptin and ghrelin, with a brief mention of resistin, visfatin and retinol-binding protein 4 among adipokines, and tumor necrosis factor-α, interleukin (IL)-6, IL-1, and briefly IL-18 among pro inflammatory cytokines.
Abstract: Nonalcoholic fatty liver disease (NAFLD) is a condition in which excess fat accumulates in the liver of a patient with no history of alcohol abuse or other causes for secondary hepatic steatosis. The pathogenesis of NAFLD and nonalcoholic steatohepatitis (NASH) has not been fully elucidated. The “two-hit“ hypothesis is probably a too simplified model to elaborate complex pathogenetic events occurring in patients with NASH. It should be better regarded as a multiple step process, with accumulation of liver fat being the first step, followed by the development of necroinflammation and fibrosis. Adipose tissue, which has emerged as an endocrine organ with a key role in energy homeostasis, is responsive to both central and peripheral metabolic signals and is itself capable of secreting a number of proteins. These adipocyte-specific or enriched proteins, termed adipokines, have been shown to have a variety of local, peripheral, and central effects. In the current review, we explore the role of adipocytokines and proinflammatory cytokines in the pathogenesis of NAFLD. We particularly focus on adiponectin, leptin and ghrelin, with a brief mention of resistin, visfatin and retinol-binding protein 4 among adipokines, and tumor necrosis factor-α, interleukin (IL)-6, IL-1, and briefly IL-18 among proinflammatory cytokines. We update their role in NAFLD, as elucidated in experimental models and clinical practice.
252 citations
10 Dec 2014
TL;DR: It seems that in the pig and humans, INTMF and VAT share a similar pattern of distribution and a similar association of components dictating insulin sensitivity, while in pigs, the relationship between leanness and higher proportions of IN TMF fat in pigs was not observed in human studies and was not corroborated by other pig studies.
Abstract: Human studies of the influence of aging and other factors on intermuscular fat (INTMF) were reviewed. Intermuscular fat increased with weight loss, weight gain, or with no weight change with age in humans. An increase in INTMF represents a similar threat to type 2 diabetes and insulin resistance as does visceral adipose tissue (VAT). Studies of INTMF in animals covered topics such as quantitative deposition and genetic relationships with other fat depots. The relationship between leanness and higher proportions of INTMF fat in pigs was not observed in human studies and was not corroborated by other pig studies. In humans, changes in muscle mass, strength and quality are associated with INTMF accretion with aging. Gene expression profiling and intrinsic methylation differences in pigs demonstrated that INTMF and VAT are primarily associated with inflammatory and immune processes. It seems that in the pig and humans, INTMF and VAT share a similar pattern of distribution and a similar association of components dictating insulin sensitivity. Studies on intramuscular (IM) adipocyte development in meat animals were reviewed. Gene expression analysis and genetic analysis have identified candidate genes involved in IM adipocyte development. Intramuscular (IM) adipocyte development in human muscle is only seen during aging and some pathological circumstance. Several genetic links between human and meat animal adipogenesis have been identified. In pigs, the Lipin1 and Lipin 2 gene have strong genetic effects on IM accumulation. Lipin1 deficiency results in immature adipocyte development in human lipodystrophy. In humans, overexpression of Perilipin 2 (PLIN2) facilitates intramyocellular lipid accretion whereas in pigs PLIN2 gene expression is associated with IM deposition. Lipins and perilipins may influence intramuscular lipid regardless of species.
120 citations
Cites background from "Gender differences in the associati..."
...The protective action of gluteal femoral SQF seems to be further limited to the femoral subcutaneous region and not necessarily with the gluteal region in black South African women further confounding the issue with ethnicity differences.(11,16,25,27,29-32) Indeed, even gender appears to have a profound influence on the responses by different adipose depots....
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...Indeed, even gender appears to have a profound influence on the responses by different adipose depots.(16,32-34) One mechanism that seems universal in human adipose depot regulation of adipose tissue is insulin, although, with as much variation within one species (human) one can only imagine the differences which exist between species....
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...Issues associated with adipose depot include disruption of normal function of organs due to infiltration with lipid-filled adipocytes—for example, nonalcoholic fatty livers are not capable of functioning as properly as normal livers, and is likely a precursor of fatty infiltration into other organs/tissues.(9,16) An interest of this paper is on the specific differences in INTMF vs....
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TL;DR: Dietary intake of natural products endowed with anti-oxidant and anti-inflammatory activities may represent a valid interventional approach for preventing and/or attenuating the pathological consequences of obesity.
Abstract: Childhood obesity is characterized by a low grade inflammation status depending on the multicellular release of cytokines, adipokines and reactive oxygen species. In particular, the imbalance between anti-inflammatory T regulatory cells and inflammatory T helper 17 cells seems to sustain such a phlogistic condition. Alterations of gut microbiota since childhood also contribute to the maintenance of inflammation. Therefore, besides preventive measures and caloric restrictions, dietary intake of natural products endowed with anti-oxidant and anti-inflammatory activities may represent a valid interventional approach for preventing and/or attenuating the pathological consequences of obesity. In this regard, the use of prebiotics, probiotics, polyphenols, polyunsaturated fatty acids, vitamins and melatonin in human clinical trials will be described.
61 citations
Cites background from "Gender differences in the associati..."
...They secrete in large amounts TNF-α, IL-6, IL-12, IL-1β, and monocyte chemotactic protein-1 (MCP-1), as well as nitric oxide (NO) (24)....
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...Adiponectin exerts anti-inflammatory activities, inhibiting IL-6 and TNF-α production (112)....
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...On the other hand, IL-1β, IL-6, and IL-8 serum levels were increased in asthmatic obese and obese children in comparison to asthmatic children and controls....
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...Treated subjects exhibited a significant reduction in weight as well as in TNF-α and IL-6 with an increase in adiponectin in comparison to the placebo group....
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...In view of its beneficial activities, melatonin has successfully been used in rats with MetS diminishing insulin resistance, release of TNF-α and IL-6 from adipocytes, low-density lipoprotein, and very low-density lipoprotein plasma levels and body weight (182)....
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TL;DR: The potential mechanisms for the migraine–obesity association are discussed, with a focus on the central and peripheral pathophysiological pathways which overlap between migraine and those modulating the drive to feed.
Abstract: Obesity and headache are both associated with a substantial personal and societal impact, and epidemiologic studies have consistently identified a positive association between obesity and headache in general, as well as obesity and migraine specifically (see part I). In the current manuscript, we will discuss the potential mechanisms for the migraine–obesity association, with a focus on the central and peripheral pathophysiological pathways which overlap between migraine and those modulating the drive to feed. We then discuss surgical, behavioral, and pharmacological treatment considerations for overweight and obese migraineurs as well as for those with idiopathic intracranial hypertension. We close by briefly discussing where future research may be headed in light of this data.
60 citations
Cites background from "Gender differences in the associati..."
...The majority of studies also support that ADP levels are inversely associated with obesity, with obese individuals having lower fasting ADP levels.(36,37) In the first trial evaluating interictal ADP levels in episodic and chronic migraineurs,(38) ADP and its multimers were measured in 37 participants (EM: 13; CM: 12; Control 12)....
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TL;DR: Higher leptin concentrations in women than in men were completely explained by differences in total body fat percentage, and visceral fat was associated with adiponectin concentrations, and did not completely explain higher adiponECTin concentrations in Women than in Men.
54 citations
References
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TL;DR: Hypoadiponectinemia is a marker for predisposition to hypertension in men and blood pressure was inversely associated with adiponectin concentration in normotensives regardless of insulin resistance.
Abstract: Adiponectin is one of the key molecules in the metabolic syndrome, and its concentration is decreased in obesity, type-2 diabetes, and coronary artery disease. Genetic investigation has revealed th...
613 citations
"Gender differences in the associati..." refers background in this paper
...Obese individuals, particularly those with accumulated visceral fat, have reduced plasma levels of adiponectin [ 1], and are at increased risk for hypertension, type 2 diabetes and atherosclerotic events [2, 3]....
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TL;DR: Elderly men and women with normal body weight may be at risk for metabolic abnormalities, including type 2 diabetes, if they possess an inordinate amount of muscle fat or visceral abdominal fat.
Abstract: OBJECTIVE —We examined whether regional adipose tissue distribution, specifically that of skeletal muscle fat and visceral abdominal fat aggregation, is characteristic of elderly individuals with hyperinsulinemia, type 2 diabetes, and impaired glucose tolerance (IGT) RESEARCH DESIGN AND METHODS —A total of 2,964 elderly men and women (mean age 736 years) were recruited for cross-sectional comparisons of diabetes or glucose tolerance, generalized obesity with dual-energy X-ray absorptiometry, and regional body fat distribution with computed tomography RESULTS —Approximately one-third of men with type 2 diabetes and less than half of women with type 2 diabetes were obese (BMI ≥30 kg/m 2 ) Despite similar amounts of subcutaneous thigh fat, intermuscular fat was higher in subjects with type 2 diabetes and IGT than in subjects with normal glucose tolerance (NGT) (112 ± 94, 103 ± 58, and 92 ± 59 cm 2 for men; 121 ± 61, 109 ± 65, and 94 ± 53 cm 2 for women; both P 2 for men; 162 ± 66, 141 ± 60, and 116 ± 54 cm 2 for women; both P 2 ) men ( r = 024 for intermuscular fat, r = 037 for visceral abdominal fat, both P r = 020 for intermuscular fat, r = 040 for visceral abdominal fat, both P CONCLUSIONS —Elderly men and women with normal body weight may be at risk for metabolic abnormalities, including type 2 diabetes, if they possess an inordinate amount of muscle fat or visceral abdominal fat
570 citations
"Gender differences in the associati..." refers background in this paper
...Variations in fat distribution mediate cardiometabolic risk factors [10]....
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TL;DR: The term "Metabolic Obesity", in reference to visceral fat accumulation in either lean or obese individuals may identify those at risk for cardiovascular disease better than the currently used definitions of obesity.
Abstract: In contrast to the accumulation of fat in the gluteo-femoral region, the accumulation of fat around abdominal viscera and inside intraabdominal solid organs is strongly associated with obesity-related complications like Type 2 diabetes and coronary artery disease. The association between visceral adiposity and accelerated atherosclerosis was shown to be independent of age, overall obesity or the amount of subcutaneous fat. Recent evidence revealed several biological and genetic differences between intraabdominal visceral-fat and peripheral subcutaneous-fat. Such differences are also reflected in their contrasting roles in the pathogenesis of obesity-related cardiometabolic problems, in either lean or obese individuals. The functional differences between visceral and the subcutaneous adipocytes may be related to their anatomical location. Visceral adipose tissue and its adipose-tissue resident macrophages produce more proinflamatory cytokines like tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) and less adiponectin. These cytokines changes induce insulin resistance and play a major role in the pathogenesis of endothelial dysfunction and subsequent atherosclerosis. The rate of visceral fat accumulation is also different according to the individual's gender and ethnic background; being more prominent in white men, African American women and Asian Indian and Japanese men and women. Such differences may explain the variation in the cardiometabolic risk at different waist measurements between different populations. However, it is unclear how much visceral fat reduction is needed to induce favorable metabolic changes. On the other hand, peripheral fat mass is negatively correlated with atherogenic metabolic risk factors and its selective reduction by liposuction does improve cardiovascular risk profile. The increasing knowledge about body fat distribution and its modifiers may lead to the development of more effective treatment strategies for people with/or at high risk for Type 2 diabetes and coronary artery disease. These accumulating observations also urge our need for a new definition of obesity based on the anatomical location of fat rather than on its volume, especially when cardiometabolic risk is considered. The term "Metabolic Obesity", in reference to visceral fat accumulation in either lean or obese individuals may identify those at risk for cardiovascular disease better than the currently used definitions of obesity.
527 citations
TL;DR: In this article, the authors examined the relationship between circulating levels of total adiponectin and the relative distribution of multimeric forms with key features of the metabolic syndrome and concluded that it is HMW quantity, not total or HMW-to-total adiponiectin ratio, that was primarily responsible for these relationships.
Abstract: Adiponectin circulates in human plasma mainly as a 180-kDa low molecular weight (LMW) hexamer and a high molecular weight (HMW) multimer of approximately 360 kDa. We comprehensively examined the relationships between circulating levels of total adiponectin, adiponectin multimers, and the relative distribution (i.e., ratio) of multimeric forms with key features of the metabolic syndrome. Total adiponectin (r = 0.45), HMW (r = 0.47), LMW (r = 0.31), and HMW-to-total adiponectin ratio (r = 0.29) were significantly correlated with insulin-stimulated glucose disposal rate. Similarly, total (r = -0.30), HMW (r = -0.38), and HMW-to-total adiponectin ratio (r = -0.34) were correlated with central fat distribution but not with total fat mass or BMI. Regarding energy metabolism, although there were no effects on resting metabolic rate, total (r = 0.41) and HMW (r = 0.44) were associated with increasing rates of fat oxidation. HMW-to-total adiponectin ratio increased as a function of total adiponectin, and it was HMW quantity (not total or HMW-to-total adiponectin ratio or LMW) that was primarily responsible for all of these relationships. Impact on nuclear magnetic resonance lipoprotein subclasses was assessed. HMW and total adiponectin were correlated with decreases in large VLDL (r = -0.44 and -0.41); decreases in small LDL (r = -0.41 and -0.36) and increases in large LDL (r = 0.36 and 0.30) particle concentrations accompanied by increased LDL particle size (r = 0.47 and 0.39); and increases in large HDL (r = 0.45 and 0.37) and HDL particle size (r = 0.53 and 0.47). Most of these correlations persisted after adjustment for metabolic covariables. In conclusion, first, serum adiponectin is associated with increased insulin sensitivity, reduced abdominal fat, and high basal lipid oxidation; however, it is HMW quantity, not total or HMW-to-total adiponectin ratio, that is primarily responsible for these relationships. Second, reduced quantities of HMW independently recapitulate the lipoprotein subclass profile associated with insulin resistance after correcting for glucose disposal rate and BMI. Finally, HMW adiponectin is an important factor in explaining the metabolic syndrome.
480 citations
TL;DR: The complex links among visceral adiposity, inflammation, and hypertension are reviewed, along with an attempt to address the clinical implications of these interactions.
Abstract: The worldwide epidemic of obesity, fostered by the modern lifestyle characterized by the lack of physical activity and an energy-dense diet, has contributed to create an unprecedented condition in human history where a majority of overfed individuals will soon surpass the number of malnourished.1 Obesity-associated disorders, such as diabetes mellitus, an atherogenic dyslipidemia, and hypertension, have undoubtedly contributed to create an atherosclerosis-prone environment and thereby the development of cardiovascular disease (CVD), a leading cause of mortality in Westernized societies. A growing body of evidence indicates that obesity is a heterogeneous condition in which body fat distribution is closely associated with metabolic perturbations and, thus, with CVD risk.2 In this regard, accumulation of visceral (intra-abdominal) fat is strongly associated with insulin resistance and with a typical atherogenic dyslipidemic state.3
The adipose tissue, once considered a simple energy warehouse, is now regarded as a complex organ not only contributing to the management of energy flux within the body but also interacting with the inflammatory system and the vascular wall. Furthermore, recent studies have underlined that there are intricate interplays among adipocytes, the sympathetic nervous system (SNS), and the renin-angiotensin system (RAS), which participate in the obesity-associated dysmetabolic state. Thus, the adipose tissue is believed to play an important role in the development of both hypertension and other complications related to insulin resistance. However, it should be pointed out that different fat depots have distinct metabolic characteristics, leading to individual differences in the impact of obesity on cardiometabolic risk. Herein, we reviewed the complex links among visceral adiposity, inflammation, and hypertension, along with an attempt to address the clinical implications of these interactions.
### Small, Dense Low-Density Lipoprotein
By its peculiar location, the expanded visceral fat depot has easy access to the liver via the portal circulation, where it could influence metabolism and promote insulin …
451 citations