Biomaterial Database

Distinct developmental profile of lower-body adipose tissue defines resistance against obesity-associated metabolic complications. 2014

Katherine E Pinnick, and George Nicholson, and Konstantinos N Manolopoulos, and Siobhán E McQuaid, and Philippe Valet, and Keith N Frayn, and Nathan Denton, and Josine L Min, and Krina T Zondervan, and Jan Fleckner, and , and Mark I McCarthy, and Chris C Holmes, and Fredrik Karpe

Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, U.K. katherine.pinnick@ocdem.ox.ac.uk fredrik.karpe@ocdem.ox.ac.uk.

Upper- and lower-body fat depots exhibit opposing associations with obesity-related metabolic disease. We defined the relationship between DEXA-quantified fat depots and diabetes/cardiovascular risk factors in a healthy population-based cohort (n = 3,399). Gynoid fat mass correlated negatively with insulin resistance after total fat mass adjustment, whereas the opposite was seen for abdominal fat. Paired transcriptomic analysis of gluteal subcutaneous adipose tissue (GSAT) and abdominal subcutaneous adipose tissue (ASAT) was performed across the BMI spectrum (n = 49; 21.4-45.5 kg/m(2)). In both depots, energy-generating metabolic genes were negatively associated and inflammatory genes were positively associated with obesity. However, associations were significantly weaker in GSAT. At the systemic level, arteriovenous release of the proinflammatory cytokine interleukin-6 (n = 34) was lower from GSAT than ASAT. Isolated preadipocytes retained a depot-specific transcriptional "memory" of embryonic developmental genes and exhibited differential promoter DNA methylation of selected genes (HOTAIR, TBX5) between GSAT and ASAT. Short hairpin RNA-mediated silencing identified TBX5 as a regulator of preadipocyte proliferation and adipogenic differentiation in ASAT. In conclusion, intrinsic differences in the expression of developmental genes in regional adipocytes provide a mechanistic basis for diversity in adipose tissue (AT) function. The less inflammatory nature of lower-body AT offers insight into the opposing metabolic disease risk associations between upper- and lower-body obesity.

UI	MeSH Term	Description	Entries
D008297	Male		Males
D008875	Middle Aged	An adult aged 45 - 64 years.	Middle Age
D009765	Obesity	A status with BODY WEIGHT that is grossly above the recommended standards, usually due to accumulation of excess FATS in the body. The standards may vary with age, sex, genetic or cultural background. In the BODY MASS INDEX, a BMI greater than 30.0 kg/m2 is considered obese, and a BMI greater than 40.0 kg/m2 is considered morbidly obese (MORBID OBESITY).
D002318	Cardiovascular Diseases	Pathological conditions involving the CARDIOVASCULAR SYSTEM including the HEART; the BLOOD VESSELS; or the PERICARDIUM.	Adverse Cardiac Event,Cardiac Events,Major Adverse Cardiac Events,Adverse Cardiac Events,Cardiac Event,Cardiac Event, Adverse,Cardiac Events, Adverse,Cardiovascular Disease,Disease, Cardiovascular,Event, Cardiac
D005260	Female		Females
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000273	Adipose Tissue	Specialized connective tissue composed of fat cells (ADIPOCYTES). It is the site of stored FATS, usually in the form of TRIGLYCERIDES. In mammals, there are two types of adipose tissue, the WHITE FAT and the BROWN FAT. Their relative distributions vary in different species with most adipose tissue being white.	Fatty Tissue,Body Fat,Fat Pad,Fat Pads,Pad, Fat,Pads, Fat,Tissue, Adipose,Tissue, Fatty
D000328	Adult	A person having attained full growth or maturity. Adults are of 19 through 44 years of age. For a person between 19 and 24 years of age, YOUNG ADULT is available.	Adults
D012307	Risk Factors	An aspect of personal behavior or lifestyle, environmental exposure, inborn or inherited characteristic, which, based on epidemiological evidence, is known to be associated with a health-related condition considered important to prevent.	Health Correlates,Risk Factor Scores,Risk Scores,Social Risk Factors,Population at Risk,Populations at Risk,Correlates, Health,Factor, Risk,Factor, Social Risk,Factors, Social Risk,Risk Factor,Risk Factor Score,Risk Factor, Social,Risk Factors, Social,Risk Score,Score, Risk,Score, Risk Factor,Social Risk Factor
D050152	Intra-Abdominal Fat	Fatty tissue inside the ABDOMINAL CAVITY, including visceral fat and retroperitoneal fat. It is the most metabolically active fat in the body and easily accessible for LIPOLYSIS. Increased visceral fat is associated with metabolic complications of OBESITY.	Abdominal Visceral Fat,Fat, Intra-Abdominal,Intra-Abdominal Adipose Tissue,Retroperitoneal Adipose Tissue,Retroperitoneal Fat,Visceral Adipose Tissue,Visceral Fat,Abdominal Visceral Fats,Adipose Tissue, Intra-Abdominal,Adipose Tissue, Retroperitoneal,Adipose Tissue, Visceral,Fat, Abdominal Visceral,Fat, Intra Abdominal,Fat, Retroperitoneal,Fat, Visceral,Fats, Abdominal Visceral,Fats, Intra-Abdominal,Fats, Retroperitoneal,Fats, Visceral,Intra Abdominal Adipose Tissue,Intra Abdominal Fat,Intra-Abdominal Fats,Retroperitoneal Fats,Visceral Fats