Disease relevance of Subcutaneous Fat

• Familial partial lipodystrophy, Dunnigan variety, (FPLD, OMIM 308980) is an autosomal-dominant condition characterized by marked loss of subcutaneous adipose tissue affecting the trunk and extremities but with excess fat deposition in the head and neck areas [1].
• These findings are consistent with the hypothesis that in diabetic pregnancy fetal hyperglycaemia and hyperinsulinism stimulate increased triglyceride synthesis in adipose cells and enlargement of adipose cells and lead to an increase in fetal subcutaneous fat [2].
• Here we show that tissue factor (TF) gene expression also is significantly elevated in the epididymal and subcutaneous fat pads from ob/ob mice compared with their lean counterparts, and that its level of expression in obese mice increases with age and the degree of obesity [3].
• METHODS: We cross-sectionally assessed lipodystrophy both clinically and radiographically in patients who, 4 years before, had been enrolled in a randomized comparative trial of stavudine- or zidovudine-based therapy. mtDNA content was measured in peripheral blood mononuclear cells (PBMCs) and subcutaneous adipose tissue from the thigh and back [4].
• During hyperglycemia, no difference was detected in delay between blood and interstitial glucose levels in subcutaneous adipose tissue (18.0 +/- 0.8 min), muscle (18.0 +/- 0.9 min), and CNS (20.3 +/- 1.2 min), respectively [5].

Psychiatry related information on Subcutaneous Fat

• The decrease in the visceral to subcutaneous fat ratio (V/S ratio) was statistically significant in the D + T group (1.09 +/- 0.11 v 0.94 +/- 0.09, P < .05), while the V/S ratio in the control group did not change [6].

High impact information on Subcutaneous Fat

• Wild-type mice fed a high-fat diet exhibited both hypersecretion of GIP and extreme visceral and subcutaneous fat deposition with insulin resistance [7].
• Plasma PAI-1 levels were closely correlated with visceral fat area but not with subcutaneous fat area in human subjects [8].
• Canthaxanthin is a synthetic, non-provitamin A carotenoid that is highly lipid-soluble; it colors the skin by deposition in the epidermis and subcutaneous fat [9].
• Similar relationships were found in human subcutaneous adipose tissue stained for the macrophage antigen CD68 [10].
• Localized overexpression of adipocyte MCSF was then induced in rabbit subcutaneous adipose tissue in vivo using adenoviral-mediated gene transfer [11].

Chemical compound and disease context of Subcutaneous Fat

• RESULTS: Patients with lipodystrophy had significantly higher 11beta-HSD1 mRNA concentrations (relative to beta2-microglobulin mRNA) in subcutaneous adipose tissue than non-lipodystrophic patients (0.29+/-0.20 vs 0.09+/-0.07, p=0.0004) and higher ratios of urinary cortisol : cortisone metabolites [12].
• CONCLUSIONS: In patients with moderate-to-severe lipodystrophy, significant improvements in subcutaneous fat continued over 104 weeks after switching from a thymidine analogue to ABC [13].
• CONCLUSIONS: Treatment with pioglitazone increased body weight, and this is associated with upregulation of some, but not all, genes previously demonstrated as "TZD responsive" in subcutaneous fat [14].
• To determine whether adipose tissue lipoprotein lipase (LPL) plays a role in the regulation of triglyceride (TG) metabolism in hypothyroidism, the activity of the enzyme was measured in the subcutaneous adipose tissue of six hypothyroid patients before and during therapy with L-thyroxine [15].
• One hundred forty-six healthy male subjects 30-71 years were evaluated for IAF and subcutaneous fat (computed tomography scan at 4th lumbar vertebra), height, body weight, % fat, various anthropometric measures, blood cholesterol (CHOL), HDL cholesterol (HDL), systolic blood pressure (SBP), and diastolic blood pressure (DBP) [16].

Biological context of Subcutaneous Fat

• At a dose corresponding to therapeutic levels in vivo (10 mg/100 ml) clofibrate also inhibited hormone-stimulated lipolysis by 20-30 percent in fragments of human subcutaneous fat [17].
• In NIDDM patients, as in control subjects, amounts of truncal subcutaneous fat showed a stronger correlation with glucose disposal rate than intraperitoneal or retroperitoneal fat; however, NIDDM patients were more insulin resistant at every level of total or regional adiposity [18].
• Insulin-induced phosphorylation of Akt also occurred to a greater extent and earlier in omental than in subcutaneous fat (P < 0.05) in the absence of significant changes in Akt protein content [19].
• Pioglitazone induces mitochondrial biogenesis in human subcutaneous adipose tissue in vivo [20].
• The pattern of ASP release from subcutaneous adipose tissue also appeared to differ in that it was significantly greater in the early postprandial period (0;-90 min) in the obese group versus the lean group and this correlated with greater triglyceride clearance during this period [21].

Anatomical context of Subcutaneous Fat

• To estimate the regional subcutaneous glycerol production rate in normal and obese humans, the venous arterialized plasma glycerol, interstitial glycerol in the subcutaneous adipose tissue together with adipose tissue blood flow (ATBF, ml/100 g.min) were measured in the postabsorptive state and for 2 h after ingestion of 100 g of oral glucose [22].
• INTERPRETATION: Adipose stromal cells from omental fat, but not subcutaneous fat, can generate active cortisol from inactive cortisone through the expression of 11 beta-HSD1 [23].
• Significantly higher HDL cholesterol values; lower triceps, scapula, and iliac subcutaneous fat thickness; and lower smoking rates were noted in all physically active groups compared with the sedentary group, whereas body mass index did not differ significantly [24].
• Triglyceride turnover in the gastrocnemius muscle was 3.3 + 1.4% over 24 h, which is about 10 times more rapid than the turnover rate in subcutaneous adipose tissue (P < 0.01) [25].
• Further investigation revealed a monoclonal gammopathy, a unique patterning of subcutaneous fat reticulation and hypodense bone marrow changes on magnetic resonance imaging (MRI), and an endocardial biopsy sample that was positive for light chain amyloid deposition [26].

Associations of Subcutaneous Fat with chemical compounds

• Glycerol production in subcutaneous adipose tissue in lean and obese humans [22].
• It is concluded that subcutaneous adipose tissue is a significant source of whole-body lactate release in the postabsorptive state and that this is further enhanced in obese subjects due to their large adipose mass [27].
• The predominant activity was oxo-reductase (conversion of cortisone to cortisol greater than cortisol to cortisone) and was higher in omental than subcutaneous fat (cortisone to cortisol, median 57.6 pmol mg-1 h-1 [95% CI 25.8-112.9] vs 0 pmol mg-1 h-1 [0-0.6], p < 0.001) [23].
• Concentration of etretinate in plasma and subcutaneous fat after long-term acitretin [28].
• Contrary to data in other patient groups, rosiglitazone did not increase subcutaneous fat in patients with HAL after 24 weeks of treatment [29].

Gene context of Subcutaneous Fat

• To elucidate the relationship between plasma levels of adiponectin, adiponectin gene expression in adipose tissue, and markers of inflammation, we obtained blood samples, anthropometric measures, and subcutaneous adipose tissue samples from 65 postmenopausal healthy women [30].
• Also, the higher expression of FOXC2 in visceral than in subcutaneous fat was restricted to subjects homozygous for the T allele (P = 0.03 vs. P = 0.7) [31].
• Protein content of extracellular signal-regulated kinase (ERK)-1/2 was threefold higher in omental than in subcutaneous fat (P < 0.05), and ERK phosphorylation showed an early 6-min peak in omental fat, in contrast with a more gradual increase observed in subcutaneous fat [19].
• Similarly, insulin was two to three times more effective in stimulating tyrosine phosphorylation of IRS-1 in subcutaneous fat cells (p < 0.01) [32].
• In vivo gene transfer to rabbit subcutaneous adipose tissue resulted in local GDNF expression for at least 2 months [33].

Analytical, diagnostic and therapeutic context of Subcutaneous Fat

• In conclusion, it is possible, using microdialysis, to directly determine the absolute glucose concentration in subcutaneous adipose tissue [34].
• Rosiglitazone treatment increases subcutaneous adipose tissue glucose uptake in parallel with perfusion in patients with type 2 diabetes: a double-blind, randomized study with metformin [35].
• IL-6 mRNA levels were measured by real-time RT-PCR in subcutaneous fat obtained from obese patients of cohort 2 during LAGB [36].
• Western blot analysis demonstrates both PR protein isoforms (human PR-A and human PR-B) in human subcutaneous adipose tissue [37].
• CONCLUSIONS: Vasoconstrictor ETB receptors appear to be present in resistance vessels isolated from subcutaneous fat in humans and from the mesentery in rats, but their contribution to endothelin mediated constriction is small, particularly in rat resistance arteries [38].

References