The Role of Adipose Tissue in Insulin Resistance in Women of African Ancestry

Abstract

Women of African ancestry, particularly those living in industrialized countries, experience a disproportionately higher prevalence of type 2 diabetes (T2D) compared to their white counterparts. Similarly, obesity and insulin resistance, which are major risk factors for T2D, are greater in black compared to white women. The exact mechanisms underlying these phenomena are not known. This paper will focus on the role of adipose tissue biology. Firstly, the characteristic body fat distribution of women of African ancestry will be discussed, followed by the depot-specific associations with insulin resistance. Factors involved in adipose tissue biology and their relation to insulin sensitivity will then be explored, including the role of sex hormones, glucocorticoid metabolism, lipolysis and adipogenesis, and their consequent effects on adipose tissue hypoxia, oxidative stress, and inflammation. Finally the role of ectopic fat deposition will be discussed. The paper proposes directions for future research, in particular highlighting the need for longitudinal and/or intervention studies to better understand the mechanisms underlying the high prevalence of insulin resistance and T2D in women of African ancestry.

Intermuscular and intramuscular adipose tissues: Bad vs. good adipose tissues

“…[1][2][3][4][5] Resident in these issues are research efforts to determine cellular and molecular control of depot-specific adipocytes, interaction, and association of adipocytes to other somatic cells, disproportionate propensities of depot-specific adipocytes to produce adipokines that function to control numerous types of body cells, and adipocyte propensity to (seemingly) disassociate themselves from normal regulatory function/control during metabolic dysfunctions such as obesity-likely as a consequence of hypoxia in the adipose depot. [2][3][4][8][9][10][11][12] Adipocytes found in different anatomical adipose depots express divergent physiologies throughout one's lifespan. 9,10,13,14 The five traditional adipose depots in animals and humans are subcutaneous (SQF), visceral (VAT), intermuscular (INTMF), intramuscular (IM), and bone adipose depots.…”

“…9,10,[18][19][20][21] A considerable number of reviews are available directing attention to preadipocyte proliferation, conversion to adipocytes and adipocyte ability to conduct lipid metabolism, produce adipokines, and become refractory to systemic signals during periods of abnormal metabolism. 4,6,[8][9][10][11]14,15,[17][18][19][20][21] Much of this knowledge was generated from studies utilizing cell lines, adipose tissue stromal vascular (SV) cell cultures, or adipose tissue slices-essentially piecing together purported mechanisms of regulation and/or marker expression during cellular conversion processes. 10,13,15,22 Knowledge pertaining to normal regulation, dysfunctional regulation, endocrine/adipokine production, and resistance of specific adipose depots to respond to metabolic signals is growing.…”

“…2,[5][6][7][8][9] Integration of these concept areas to provide a mechanism with which to target for clinical remediation of the adverse symptoms of adipose tissue manifestations is lacking, however, possibly due to conflicting messages about adipose origins, the obese phenotype, its causes, and repercussions. [10][11][12][13][14] Indeed, it appears that the preponderance of evidence states that SQF adiposity supplies a measure of protection against metabolic dysregulation, whereas VAT is considered a source of dysregulation (especially insulin resistance). 2,[15][16][17][18][19][20][21][22][23] However, this message is further muddied by new reports that demonstrate that truncal SQF adipose tissue may actually aid in the metabolic changes that occur with obesity as this depot supplies a greater percentage of adipose tissue compared with the VAT and that the protective effects of SQ fat is limited more to the gluteal femoral SQ depot (or the so-called "pear-shape").…”

“…2,[15][16][17][18][19][20][21][22][23] However, this message is further muddied by new reports that demonstrate that truncal SQF adipose tissue may actually aid in the metabolic changes that occur with obesity as this depot supplies a greater percentage of adipose tissue compared with the VAT and that the protective effects of SQ fat is limited more to the gluteal femoral SQ depot (or the so-called "pear-shape"). 11,15,[24][25][26][27][28] 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][30][31][32] Indeed, even gender appears to have a profound influence on the responses by different adipose depots.…”

“…11,15,[24][25][26][27][28] 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][30][31][32] Indeed, even gender appears to have a profound influence on the responses by different adipose depots. 16,[32][33][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.…”