Developmental origin of adipocytes: new insights into a pending question

Billon, Noëlle; Monteiro, Miguel Caetano; Dani, Christian

doi:10.1042/bc20080011

Cited by 86 publications

(63 citation statements)

References 82 publications

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“…Indeed, intraabdominal/visceral fat accumulation is associated with a higher risk of diabetes and metabolic syndrome, whereas increased s.c. fat in the thighs and hips may even have a protective effect (4,8,26). A growing body of evidence suggests that these depot-specific associations are due to intrinsic differences in the properties of adipocytes in each depot (27,28) and the consequence of a divergence in their developmental origin (1,(9)(10)(11)(12)29). Consistent with this hypothesis, we and others observed high differential expression of developmental genes between intraabdominal and s.c. adipose depots in both rodents and humans (11,12).…”

Section: Discussionsupporting

confidence: 75%

Mesodermal developmental gene Tbx15 impairs adipocyte differentiation and mitochondrial respiration

Gesta

Bézy²,

Mori³

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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Increased intraabdominal (visceral) fat is associated with a high risk of diabetes and metabolic syndrome. We have previously shown that the mesodermal developmental transcription factor Tbx15 is highly differentially expressed between visceral and subcutaneous (s.c.) fat in both humans and rodents, and in humans visceral fat Tbx15 expression is decreased in obesity. Here we show that, in mice, Tbx15 is 260-fold more highly expressed in s.c. preadipocytes than in epididymal preadipocytes. Overexpression of Tbx15 in 3T3-L1 preadipocytes impairs adipocyte differentiation and decreases triglyceride content. This defect in differentiation can be corrected by stimulating cells with the PPARγ agonist rosiglitazone (Rosi). However, triglyceride accumulation remains decreased by ∼50%, due to a decrease in basal lipogenic rate and increase in basal lipolytic rate. 3T3-L1 preadipocytes overexpressing Tbx15 also have a 15% reduction in mitochondrial mass and a 28% reduction in basal mitochondrial respiration (P = 0.004) and ATP turnover (P = 0.02), and a 45% (P = 0.003) reduction in mitochondrial respiratory capacity. Thus, differential expression of Tbx15 between fat depots plays an important role in the interdepot differences in adipocyte differentiation, triglyceride accumulation, and mitochondrial function that may contribute to the risk of diabetes and metabolic disease.thiazolidinedione | bioenergetics profile | Oil Red O

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Section: Discussionsupporting

confidence: 75%

Mesodermal developmental gene Tbx15 impairs adipocyte differentiation and mitochondrial respiration

Gesta

Bézy²,

Mori³

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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“…The gaps in our knowledge of adipogenesis are exemplifi ed by the fact that the developmental origins of MSCs and their adipocyte progeny have not been fully resolved. Similarly, the genetic and cellular mechanisms controlling development of MSCs and adipocytes in vivo remain largely unknown ( 2,17 ). These important gaps in our knowledge can be attributed in part to the inherent limitations and challenges of available mammalian model systems.…”

Section: Animals and Experimental Conditionsmentioning

confidence: 99%

Ontogeny and nutritional control of adipogenesis in zebrafish (Danio rerio)

Flynn¹,

Trent²,

Rawls

2009

Journal of Lipid Research

203

246

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storage of energy as neutral lipid (i.e., triacylglycerol) in adipose tissues. Storing excess energy as neutral lipid is an evolutionarily conserved characteristic common to virtually all animals, providing a valuable energy source during periods of nutrient scarcity ( 2, 3 ). Vertebrates are capable of storing neutral lipid in several tissues, with adipose tissue serving as the primary depot. The principal cellular component of adipose tissue is the adipocyte, a cell type specialized for storing fat in cytoplasmic neutral lipid droplets and endocrine control of energy balance ( 4, 5 ).Current knowledge of adipocyte development and physiology is largely derived from research using mammalian model systems. Mammals develop two general types of adipose tissues: white adipose tissue (WAT) and brown adipose tissue (BAT). WAT is more abundant and serves primarily as a site of energy storage and mobilization, while BAT primarily functions in energy expenditure in the form of thermogenesis. WAT and BAT form in distinct anatomic depots during mammalian development, with different depots displaying distinctive patterns of gene expression, endocrine sensitivity, and association with metabolic diseases ( 2 ). Adipocytes within WAT (white adipocytes) and BAT (brown adipocytes) both contain cytoplasmic neutral lipid droplets; however, mature white adipocytes typically contain a single large droplet (unilocular), while brown adipocytes contain multiple smaller lipid droplets. Previous studies have indicated that adipocytes develop from multipotent mesenchymal stem cells (MSCs). MSCs are classically considered to be derived from the mesoderm, although recent studies suggest that MSCs have additional developmental origins, such as the neural crest or neuroepithelium ( 6, 7 ). In addition to producing adipocytes during development, MSCs are thought to populate distinct anatomical sites in adult animals, including bone The worldwide epidemic of obesity and associated complications, such as type II diabetes, hypertension, and cardiovascular disease, has resulted in the designation of obesity as a major public health challenge of our time ( 1 ). Obesity is a disorder of energy imbalance in which an excess of energy intake over expenditure leads to increased This work was funded

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“…In contrast with muscles, the developmental processes leading to the formation of mature adipose tissue cells (adipocytes) are poorly understood; however, some recent work has given insights into this process (Billon et al 2008;Berry et al 2013). In general, adipocytes can be divided into two types: white and brown.…”

Section: Evidence For Programming Of Body Fatmentioning

confidence: 99%

Epigenetics and developmental programming of welfare and production traits in farm animals

Sinclair

Rutherford

Wallace

et al. 2016

Reprod. Fertil. Dev.

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Abstract. The concept that postnatal health and development can be influenced by events that occur in utero originated from epidemiological studies in humans supported by numerous mechanistic (including epigenetic) studies in a variety of model species. Referred to as the 'developmental origins of health and disease' or 'DOHaD' hypothesis, the primary focus of large-animal studies until quite recently had been biomedical. Attention has since turned towards traits of commercial importance in farm animals. Herein we review the evidence that prenatal risk factors, including suboptimal parental nutrition, gestational stress, exposure to environmental chemicals and advanced breeding technologies, can determine traits such as postnatal growth, feed efficiency, milk yield, carcass composition, animal welfare and reproductive potential. We consider the role of epigenetic and cytoplasmic mechanisms of inheritance, and discuss implications for livestock production and future research endeavours. We conclude that although the concept is proven for several traits, issues relating to effect size, and hence commercial importance, remain. Studies have also invariably been conducted under controlled experimental conditions, frequently assessing single risk factors, thereby limiting their translational value for livestock production. We propose concerted international research efforts that consider multiple, concurrent stressors to better represent effects of contemporary animal production systems.

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Developmental origin of adipocytes: new insights into a pending question

Cited by 86 publications

References 82 publications

Mesodermal developmental gene Tbx15 impairs adipocyte differentiation and mitochondrial respiration

Mesodermal developmental gene Tbx15 impairs adipocyte differentiation and mitochondrial respiration

Ontogeny and nutritional control of adipogenesis in zebrafish (Danio rerio)

Epigenetics and developmental programming of welfare and production traits in farm animals

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