Scholars@Duke
Rana K. Gupta

Rana K. Gupta

W. David and Sarah W. Stedman Distinguished Professor
Medicine, Endocrinology, Metabolism, and Nutrition

Selected Publications

The Expanding Problem of Regional Adiposity: Revisiting a 1985 Diabetes Classic by Ohlson et al.

Journal Article Diabetes · May 1, 2024 Body fat distribution is a predictor of metabolic health in obesity. In this Classics in Diabetes article, we revisit a 1985 Diabetes article by Swedish investigators Ohlson et al. This work was one of the first prospective population-based studies that es ... Full text Link to item Cite

GPR84-mediated signal transduction affects metabolic function by promoting brown adipocyte activity.

Journal Article J Clin Invest · December 15, 2023 The G protein-coupled receptor 84 (GPR84), a medium-chain fatty acid receptor, has garnered attention because of its potential involvement in a range of metabolic conditions. However, the precise mechanisms underlying this effect remain elusive. Our study ... Full text Link to item Cite

Protocol for quantitative proteomic analysis of heterogeneous adipose tissue-residing progenitor subpopulations in mice.

Journal Article STAR Protoc · December 15, 2023 Recent studies have revealed cellular heterogeneity of mesenchymal stromal cells and immune cells in adipose tissue and emphasized the need for quantitative analysis of small numbers of functionally distinct cells using state-of-the-art "omics" technologie ... Full text Link to item Cite

Mesenchymal stromal cells as conductors of adipose tissue remodeling.

Journal Article Genes Dev · September 1, 2023 Adipose tissue exhibits a remarkable capacity to expand, contract, and remodel in response to changes in physiological and environmental conditions. Here, we describe recent advances in our understanding of how functionally distinct tissue-resident mesench ... Full text Link to item Cite

Adipose tissue at single-cell resolution.

Journal Article Cell metabolism · March 2023 Adipose tissue exhibits remarkable plasticity with capacity to change in size and cellular composition under physiological and pathophysiological conditions. The emergence of single-cell transcriptomics has rapidly transformed our understanding of the dive ... Full text Cite

GPR92 activation in islet macrophages controls β cell function in a diet-induced obesity model.

Journal Article J Clin Invest · November 1, 2022 The molecular mechanisms underlying obesity-induced increases in β cell mass and the resulting β cell dysfunction need to be elucidated further. Our study revealed that GPR92, expressed in islet macrophages, is modulated by dietary interventions in metabol ... Full text Link to item Cite

Time-restricted feeding mitigates obesity through adipocyte thermogenesis.

Journal Article Science · October 21, 2022 Misalignment of feeding rhythms with the light-dark cycle leads to disrupted peripheral circadian clocks and obesity. Conversely, restricting feeding to the active period mitigates metabolic syndrome through mechanisms that remain unknown. We found that ge ... Full text Link to item Cite

Adipocyte mesenchymal transition contributes to mammary tumor progression.

Journal Article Cell Rep · September 13, 2022 Obesity is associated with increased cancer incidence and progression. However, the relationship between adiposity and cancer remains poorly understood at the mechanistic level. Here, we report that adipocytes from tumor-invasive mammary fat undergo de-dif ... Full text Link to item Cite

Distinct functional properties of murine perinatal and adult adipose progenitor subpopulations.

Journal Article Nat Metab · August 2022 Adult white adipose tissue (WAT) harbors distinct mesenchymal stromal cell subpopulations that differentially affect WAT function and plasticity. Here we unveil the cellular landscape of the perinatal epididymal WAT primordium using single-cell transcripto ... Full text Link to item Cite

Multilayered omics reveal sex- and depot-dependent adipose progenitor cell heterogeneity.

Journal Article Cell Metab · May 3, 2022 Single-cell RNA sequencing (scRNA-seq) has revealed that adult white adipose tissue (WAT) harbors functionally diverse subpopulations of mesenchymal stromal cells that differentially impact tissue plasticity. To date, the molecular basis of this cellular h ... Full text Link to item Cite

ZFP423 controls EBF2 coactivator recruitment and PPARγ occupancy to determine the thermogenic plasticity of adipocytes.

Journal Article Genes Dev · November 1, 2021 Energy-storing white adipocytes maintain their identity by suppressing the energy-burning thermogenic gene program of brown and beige adipocytes. Here, we reveal that the protein-protein interaction between the transcriptional coregulator ZFP423 and brown ... Full text Link to item Cite

Cold-responsive adipocyte progenitors couple adrenergic signaling to immune cell activation to promote beige adipocyte accrual.

Journal Article Genes Dev · October 1, 2021 The full array of cold-responsive cell types within white adipose tissue that drive thermogenic beige adipocyte biogenesis remains undefined. We demonstrate that acute cold challenge elicits striking transcriptomic changes specifically within DPP4+ PDGFRβ+ ... Full text Link to item Cite

Adipose tissue hyaluronan production improves systemic glucose homeostasis and primes adipocytes for CL 316,243-stimulated lipolysis.

Journal Article Nat Commun · August 10, 2021 Plasma hyaluronan (HA) increases systemically in type 2 diabetes (T2D) and the HA synthesis inhibitor, 4-Methylumbelliferone, has been proposed to treat the disease. However, HA is also implicated in normal physiology. Therefore, we generated a Hyaluronan ... Full text Link to item Cite

Regulation of cold-induced thermogenesis by the RNA binding protein FAM195A.

Journal Article Proc Natl Acad Sci U S A · June 8, 2021 Homeothermic vertebrates produce heat in cold environments through thermogenesis, in which brown adipose tissue (BAT) increases mitochondrial oxidation along with uncoupling of the electron transport chain and activation of uncoupling protein 1 (UCP1). Alt ... Full text Link to item Cite

Adiponectin preserves metabolic fitness during aging.

Journal Article Elife · April 27, 2021 Adiponectin is essential for the regulation of tissue substrate utilization and systemic insulin sensitivity. Clinical studies have suggested a positive association of circulating adiponectin with healthspan and lifespan. However, the direct effects of adi ... Full text Link to item Cite

Mitochondrial metabolism is a key regulator of the fibro-inflammatory and adipogenic stromal subpopulations in white adipose tissue.

Journal Article Cell Stem Cell · April 1, 2021 The adipose tissue stroma is a rich source of molecularly distinct stem and progenitor cell populations with diverse functions in metabolic regulation, adipogenesis, and inflammation. The ontology of these populations and the mechanisms that govern their b ... Full text Link to item Cite

Pathologic HIF1α signaling drives adipose progenitor dysfunction in obesity.

Journal Article Cell Stem Cell · April 1, 2021 Adipose precursor cells (APCs) exhibit regional variation in response to obesity, for unclear reasons. Here, we reveal that HIFα-induced PDGFRβ signaling within murine white adipose tissue (WAT) PDGFRβ+ cells drives inhibitory serine 112 (S112) phosphoryla ... Full text Link to item Cite

Perivascular mesenchymal cells control adipose-tissue macrophage accrual in obesity.

Journal Article Nat Metab · November 2020 Chronic low-grade white adipose tissue (WAT) inflammation is a hallmark of metabolic syndrome in obesity. Here, we demonstrate that a subpopulation of mouse WAT perivascular (PDGFRβ+) cells, termed fibro-inflammatory progenitors (FIPs), activate proinflamm ... Full text Link to item Cite

Functional Interplay between Histone H2B ADP-Ribosylation and Phosphorylation Controls Adipogenesis.

Journal Article Mol Cell · September 17, 2020 Although ADP-ribosylation of histones by PARP-1 has been linked to genotoxic stress responses, its role in physiological processes and gene expression has remained elusive. We found that NAD+-dependent ADP-ribosylation of histone H2B-Glu35 by small nucleol ... Full text Link to item Cite

Isolation of Adipogenic and Fibro-Inflammatory Stromal Cell Subpopulations from Murine Intra-Abdominal Adipose Depots.

Journal Article J Vis Exp · August 16, 2020 The stromal-vascular fraction (SVF) of white adipose tissue (WAT) is remarkably heterogeneous and consists of numerous cell types that contribute functionally to the expansion and remodeling of WAT in adulthood. A tremendous barrier to studying the implica ... Full text Link to item Cite

Dermal adipose tissue has high plasticity and undergoes reversible dedifferentiation in mice.

Journal Article J Clin Invest · December 2, 2019 Dermal adipose tissue (also known as dermal white adipose tissue and herein referred to as dWAT) has been the focus of much discussion in recent years. However, dWAT remains poorly characterized. The fate of the mature dermal adipocytes and the origin of t ... Full text Link to item Cite

Contribution of adipogenesis to healthy adipose tissue expansion in obesity.

Journal Article J Clin Invest · October 1, 2019 The manner in which white adipose tissue (WAT) expands and remodels directly impacts the risk of developing metabolic syndrome in obesity. Preferential accumulation of visceral WAT is associated with increased risk for insulin resistance, whereas subcutane ... Full text Link to item Cite

Cellular Origins of Beige Fat Cells Revisited.

Journal Article Diabetes · October 2019 Activated beige adipocytes have therapeutic potential due to their ability to improve glucose and lipid homeostasis. To date, the origin of beige adipocytes remains enigmatic. Whether beige cells arise through de novo differentiation from resident precurso ... Full text Link to item Cite

A PRDM16-Driven Metabolic Signal from Adipocytes Regulates Precursor Cell Fate.

Journal Article Cell Metab · July 2, 2019 The precursor cells for metabolically beneficial beige adipocytes can alternatively become fibrogenic and contribute to adipose fibrosis. We found that cold exposure or β3-adrenergic agonist treatment of mice decreased the fibrogenic profile of precursor c ... Full text Link to item Cite

The next decade of metabolism.

Journal Article Nat Metab · January 2019 Full text Link to item Cite

Transcriptional brakes on the road to adipocyte thermogenesis.

Journal Article Biochim Biophys Acta Mol Cell Biol Lipids · January 2019 White adipocytes represent the principle site for energy storage whereas brown/beige adipocytes emerge from seemingly distinct cellular lineages and burn chemical energy to produce heat. Thermogenic adipocytes utilize cell-type selective master regulatory ... Full text Link to item Cite

Regulator of Calcineurin 1 helps coordinate whole-body metabolism and thermogenesis.

Journal Article EMBO Rep · December 2018 Increasing non-shivering thermogenesis (NST), which expends calories as heat rather than storing them as fat, is championed as an effective way to combat obesity and metabolic disease. Innate mechanisms constraining the capacity for NST present a fundament ... Full text Link to item Cite

Identification of functionally distinct fibro-inflammatory and adipogenic stromal subpopulations in visceral adipose tissue of adult mice.

Journal Article Elife · September 28, 2018 UNLABELLED: White adipose tissue (WAT) remodeling is dictated by coordinated interactions between adipocytes and resident stromal-vascular cells; however, the functional heterogeneity of adipose stromal cells has remained unresolved. We combined single-cel ... Full text Link to item Cite

Reversible De-differentiation of Mature White Adipocytes into Preadipocyte-like Precursors during Lactation.

Journal Article Cell Metab · August 7, 2018 Adipose tissue in the mammary gland undergoes dramatic remodeling during reproduction. Adipocytes are replaced by mammary alveolar structures during pregnancy and lactation, then reappear upon weaning. The fate of the original adipocytes during lactation a ... Full text Link to item Cite

Role of Fractionated Fat in Blending the Lid-Cheek Junction.

Journal Article Plast Reconstr Surg · July 2018 BACKGROUND: Fat grafting has been used extensively in plastic surgery in the past two decades. Here, the authors report the retrospective comparison of patients who underwent fractionated fat injection to blend the lid-cheek junction with those who had reg ... Full text Link to item Cite

Peroxisome Proliferator-Activated Receptor γ and Its Role in Adipocyte Homeostasis and Thiazolidinedione-Mediated Insulin Sensitization.

Journal Article Mol Cell Biol · May 15, 2018 Adipose tissue is a dynamic organ that makes critical contributions to whole-body metabolic homeostasis. Although recent studies have revealed that different fat depots have distinct molecular signatures, metabolic functions and adipogenic mechanisms, pero ... Full text Link to item Cite

Warming Induces Significant Reprogramming of Beige, but Not Brown, Adipocyte Cellular Identity.

Journal Article Cell Metab · May 1, 2018 Beige and brown adipocytes generate heat in response to reductions in ambient temperature. When warmed, both beige and brown adipocytes exhibit morphological "whitening," but it is unknown whether or to what extent this represents a true shift in cellular ... Full text Link to item Cite

Adipocyte Xbp1s overexpression drives uridine production and reduces obesity.

Journal Article Mol Metab · May 2018 OBJECTIVE: The spliced transcription factor Xbp1 (Xbp1s), a transducer of the unfolded protein response (UPR), regulates lipolysis. Lipolysis is stimulated by fasting when uridine synthesis is also activated in adipocytes. METHODS: Here we have examined th ... Full text Link to item Cite

Acute loss of adipose tissue-derived adiponectin triggers immediate metabolic deterioration in mice.

Journal Article Diabetologia · April 2018 AIM/HYPOTHESIS: Adiponectin (APN), a circulating hormone secreted by mature adipocytes, has been extensively studied because it has beneficial metabolic effects. While many studies have focused on the congenital loss of APN and its effects on systemic body ... Full text Link to item Cite

De novo adipocyte differentiation from Pdgfrβ+ preadipocytes protects against pathologic visceral adipose expansion in obesity.

Journal Article Nat Commun · March 1, 2018 Pathologic expansion of white adipose tissue (WAT) in obesity is characterized by adipocyte hypertrophy, inflammation, and fibrosis; however, factors triggering this maladaptive remodeling are largely unknown. Here, we test the hypothesis that the potentia ... Full text Link to item Cite

Intracellular lipid metabolism impairs β cell compensation during diet-induced obesity.

Journal Article J Clin Invest · March 1, 2018 The compensatory proliferation of insulin-producing β cells is critical to maintaining glucose homeostasis at the early stage of type 2 diabetes. Failure of β cells to proliferate results in hyperglycemia and insulin dependence in patients. To understand t ... Full text Link to item Cite

An Adipose Tissue Atlas: An Image-Guided Identification of Human-like BAT and Beige Depots in Rodents.

Journal Article Cell Metab · January 9, 2018 [18F]Fluorodeoxyglucose-PET/CT (18F-FDG-PET/CT) imaging has been invaluable for visualizing metabolically active adipose tissues in humans with potential anti-diabetic and anti-obesity effects. To explore whether mice display human-like fat depots in anato ... Full text Link to item Cite

Hepatic GALE Regulates Whole-Body Glucose Homeostasis by Modulating Tff3 Expression.

Journal Article Diabetes · November 2017 Transcripts of key enzymes in the Leloir pathway of galactose metabolism in mouse livers are significantly increased after chronic high-fat/high-sucrose feeding. UDP-galactose-4-epimerase (GALE) is the last enzyme in this pathway that converts UDP-galactos ... Full text Link to item Cite

Directing visceral white adipocyte precursors to a thermogenic adipocyte fate improves insulin sensitivity in obese mice.

Journal Article Elife · July 19, 2017 Visceral adiposity confers significant risk for developing metabolic disease in obesity whereas preferential expansion of subcutaneous white adipose tissue (WAT) appears protective. Unlike subcutaneous WAT, visceral WAT is resistant to adopting a protectiv ... Full text Link to item Cite

Do Adipocytes Emerge from Mural Progenitors?

Journal Article Cell Stem Cell · May 4, 2017 Gupta and colleagues highlight recent work, including their own, that suggested based on lineage tracing that mural cells are adipogenic, contrasting with the conclusions of a recent Cell Stem Cell paper. ... Full text Link to item Cite

The expanding problem of adipose depot remodeling and postnatal adipocyte progenitor recruitment.

Journal Article Mol Cell Endocrinol · April 15, 2017 The rising incidence of obesity and associated metabolic diseases has increased the urgency in understanding all aspects of adipose tissue biology. This includes the function of adipocytes, how adipose tissue expands in obesity, and how expanded adipose ti ... Full text Link to item Cite

Regeneration of fat cells from myofibroblasts during wound healing.

Journal Article Science · February 17, 2017 Although regeneration through the reprogramming of one cell lineage to another occurs in fish and amphibians, it has not been observed in mammals. We discovered in the mouse that during wound healing, adipocytes regenerate from myofibroblasts, a cell type ... Full text Link to item Cite

PARP-1 Controls the Adipogenic Transcriptional Program by PARylating C/EBPβ and Modulating Its Transcriptional Activity.

Journal Article Mol Cell · January 19, 2017 Poly(ADP-ribosyl)ation (PARylation) is a post-translational modification of proteins mediated by PARP family members, such as PARP-1. Although PARylation has been studied extensively, few examples of definitive biological roles for site-specific PARylation ... Full text Link to item Cite

Sorting out adipocyte precursors and their role in physiology and disease.

Journal Article Genes Dev · January 15, 2017 The ability to maintain and expand the pool of adipocytes in adults is integral to the regulation of energy balance, tissue/stem cell homeostasis, and disease pathogenesis. For decades, our knowledge of adipocyte precursors has relied on cellular models. T ... Full text Link to item Cite

Fetal development of subcutaneous white adipose tissue is dependent on Zfp423.

Journal Article Mol Metab · January 2017 OBJECTIVE: Zfp423 is a multi zinc-finger transcription factor expressed in preadipocytes and mature adipocytes in vivo. Our recent work has revealed a critical role for Zfp423 in maintaining the fate of white adipocytes in adult mice through suppression of ... Full text Link to item Cite

Connexin 43 Mediates White Adipose Tissue Beiging by Facilitating the Propagation of Sympathetic Neuronal Signals.

Journal Article Cell Metab · September 13, 2016 "Beige" adipocytes reside in white adipose tissue (WAT) and dissipate energy as heat. Several studies have shown that cold temperature can activate pro-opiomelanocortin-expressing (POMC) neurons and increase sympathetic neuronal tone to regulate WAT beigin ... Full text Link to item Cite

Zfp423 Maintains White Adipocyte Identity through Suppression of the Beige Cell Thermogenic Gene Program.

Journal Article Cell Metab · June 14, 2016 The transcriptional regulators Ebf2 and Prdm16 establish and maintain the brown and/or beige fat cell identity. However, the mechanisms operating in white adipocytes to suppress the thermogenic gene program and maintain an energy-storing phenotype are less ... Full text Link to item Cite

Pdgfrβ+ Mural Preadipocytes Contribute to Adipocyte Hyperplasia Induced by High-Fat-Diet Feeding and Prolonged Cold Exposure in Adult Mice.

Journal Article Cell Metab · February 9, 2016 The expansion of white adipose tissue (WAT) in obesity involves de novo differentiation of new adipocytes; however, the cellular origin of these cells remains unclear. Here, we utilize Zfp423(GFP) reporter mice to characterize adipose mural (Pdgfrβ(+)) cel ... Full text Link to item Cite

Impact of tamoxifen on adipocyte lineage tracing: Inducer of adipogenesis and prolonged nuclear translocation of Cre recombinase.

Journal Article Mol Metab · November 2015 BACKGROUND: The selective estrogen receptor modulator tamoxifen, in combination with the Cre-ER(T2) fusion protein, has been one of the mainstream methods to induce genetic recombination and has found widespread application in lineage tracing studies. METH ... Full text Link to item Cite

Visceral Adipose Tissue Mesothelial Cells: Living on the Edge or Just Taking Up Space?

Journal Article Trends Endocrinol Metab · October 2015 Visceral adiposity and pathological adipose tissue remodeling, a result of overnutrition, are strong predictors of metabolic health in obesity. Factors intrinsic to visceral adipose depots are likely to play a causal role in eliciting the detrimental effec ... Full text Link to item Cite

Distinct regulatory mechanisms governing embryonic versus adult adipocyte maturation.

Journal Article Nat Cell Biol · September 2015 Pathological expansion of adipose tissue contributes to the metabolic syndrome. Distinct depots develop at various times under different physiological conditions. The transcriptional cascade mediating adipogenesis is established in vitro, and centres aroun ... Full text Link to item Cite

Activation of natriuretic peptides and the sympathetic nervous system following Roux-en-Y gastric bypass is associated with gonadal adipose tissues browning.

Journal Article Mol Metab · May 2015 OBJECTIVE: Roux-en-Y gastric bypass (RYGB) is an effective method of weight loss and remediation of type-2 diabetes; however, the mechanisms leading to these improvements are unclear. Additionally, adipocytes within white adipose tissue (WAT) depots can ma ... Full text Link to item Cite

CREB mediates the insulinotropic and anti-apoptotic effects of GLP-1 signaling in adult mouse β-cells.

Journal Article Mol Metab · November 2014 OBJECTIVE: Glucagon-like peptide-1 (GLP-1) plays a major role in pancreatic β-cell function and survival by increasing cytoplasmic cAMP levels, which are thought to affect transcription through activation of the basic leucine zipper (bZIP) transcription fa ... Full text Link to item Cite

Adiponectin is essential for lipid homeostasis and survival under insulin deficiency and promotes β-cell regeneration.

Journal Article Elife · October 23, 2014 As an adipokine in circulation, adiponectin has been extensively studied for its beneficial metabolic effects. While many important functions have been attributed to adiponectin under high-fat diet conditions, little is known about its essential role under ... Full text Link to item Cite

Adipocytes.

Journal Article Curr Biol · October 20, 2014 Full text Link to item Cite

ERα upregulates Phd3 to ameliorate HIF-1 induced fibrosis and inflammation in adipose tissue.

Journal Article Mol Metab · September 2014 Hypoxia Inducible Factor 1 (HIF-1) promotes fibrosis and inflammation in adipose tissues, while estrogens and Estrogen Receptor α (ERα) have the opposite effect. Here we identify an Estrogen Response Element (ERE) in the promoter of Phd3, which is a negati ... Full text Link to item Cite

Elevated resistin levels induce central leptin resistance and increased atherosclerotic progression in mice.

Journal Article Diabetologia · June 2014 AIMS/HYPOTHESIS: Resistin was originally identified as an adipocyte-derived factor upregulated during obesity and as a contributor to obesity-associated insulin resistance. Clinically, resistin has also been implicated in cardiovascular disease in a number ... Full text Link to item Cite

Improved methodologies for the study of adipose biology: insights gained and opportunities ahead.

Journal Article J Lipid Res · April 2014 Adipocyte differentiation and function have become areas of intense focus in the field of energy metabolism; however, understanding the role of specific genes in the establishment and maintenance of fat cell function can be challenging and complex. In this ... Full text Link to item Cite

Tracking adipogenesis during white adipose tissue development, expansion and regeneration.

Journal Article Nat Med · October 2013 White adipose tissue displays high plasticity. We developed a system for the inducible, permanent labeling of mature adipocytes that we called the AdipoChaser mouse. We monitored adipogenesis during development, high-fat diet (HFD) feeding and cold exposur ... Full text Link to item Cite

TRPV4 is a regulator of adipose oxidative metabolism, inflammation, and energy homeostasis.

Journal Article Cell · September 28, 2012 PGC1α is a key transcriptional coregulator of oxidative metabolism and thermogenesis. Through a high-throughput chemical screen, we found that molecules antagonizing the TRPVs (transient receptor potential vanilloid), a family of ion channels, induced PGC1 ... Full text Link to item Cite

Zfp423 expression identifies committed preadipocytes and localizes to adipose endothelial and perivascular cells.

Journal Article Cell Metab · February 8, 2012 Progress has been made in elucidating the cell-surface phenotype of primary adipose progenitors; however, specific functional markers and distinct molecular signatures of fat depot-specific preadipocytes have remained elusive. In this study, we label commi ... Full text Link to item Cite

Regulation of early adipose commitment by Zfp521.

Journal Article PLoS Biol · 2012 While there has been significant progress in determining the transcriptional cascade involved in terminal adipocyte differentiation, less is known about early events leading to lineage commitment and cell fate choice. It has been recently discovered that z ... Full text Link to item Cite

Identifying novel transcriptional components controlling energy metabolism.

Journal Article Cell Metab · December 7, 2011 The investigation of metabolic regulation at the transcriptional level presents different challenges than those encountered in the study of other important problems like development or cancer. Levels of key components like glucose, insulin, and lipids can ... Full text Link to item Cite

C/EBPβ controls exercise-induced cardiac growth and protects against pathological cardiac remodeling.

Journal Article Cell · December 23, 2010 The heart has the ability to grow in size in response to exercise, but little is known about the transcriptional mechanisms underlying physiological hypertrophy. Adult cardiomyocytes have also recently been proven to hold the potential for proliferation, a ... Full text Link to item Cite

PGC-1alpha regulates a HIF2alpha-dependent switch in skeletal muscle fiber types.

Journal Article Proc Natl Acad Sci U S A · December 14, 2010 The coactivator peroxisome proliferator-activated receptor-gamma coactivator 1 α (PGC-1α) coordinates a broad set of transcriptional programs that regulate the response of skeletal muscle to exercise. However, the complete transcriptional network controlle ... Full text Link to item Cite

Transcriptional control of preadipocyte determination by Zfp423.

Journal Article Nature · March 25, 2010 The worldwide epidemic of obesity has increased the urgency to develop a deeper understanding of physiological systems related to energy balance and energy storage, including the mechanisms controlling the development of fat cells (adipocytes). The differe ... Full text Link to item Cite

Role of insulin-like growth factor-binding protein 5 (IGFBP5) in organismal and pancreatic beta-cell growth.

Journal Article Mol Endocrinol · January 2010 A family of IGF-binding proteins (IGFBP) exerts biological actions both dependent on and independent of IGF-I. A major effector of the insulin/IGF-I signaling pathway, the serine/threonine protein kinase Akt, mediates cellular processes such as glucose upt ... Full text Link to item Cite

The transcriptional coactivator PGC-1alpha mediates exercise-induced angiogenesis in skeletal muscle.

Journal Article Proc Natl Acad Sci U S A · December 15, 2009 Peripheral arterial disease (PAD) affects 5 million people in the US and is the primary cause of limb amputations. Exercise remains the single best intervention for PAD, in part thought to be mediated by increases in capillary density. How exercise trigger ... Full text Link to item Cite

The transcriptional response of the islet to pregnancy in mice.

Journal Article Mol Endocrinol · October 2009 The inability of the ss-cell to meet the demand for insulin brought about by insulin resistance leads to type 2 diabetes. In adults, ss-cell replication is one of the mechanisms thought to cause the expansion of ss-cell mass. Efforts to treat diabetes requ ... Full text Link to item Cite

Expansion of adult beta-cell mass in response to increased metabolic demand is dependent on HNF-4alpha.

Journal Article Genes Dev · April 1, 2007 The failure to expand functional pancreatic beta-cell mass in response to increased metabolic demand is a hallmark of type 2 diabetes. Lineage tracing studies indicate that replication of existing beta-cells is the principle mechanism for beta-cell expansi ... Full text Link to item Cite

Foxa1-deficient mice exhibit impaired insulin secretion due to uncoupled oxidative phosphorylation.

Journal Article Diabetes · October 2006 Foxa1 (formerly hepatic nuclear factor 3alpha) belongs to the family of Foxa genes that are expressed in early development and takes part in the differentiation of endoderm-derived organs and the regulation of glucose homeostasis. Foxa1-/- pups are growth ... Full text Link to item Cite

The MODY1 gene HNF-4alpha regulates selected genes involved in insulin secretion.

Journal Article J Clin Invest · April 2005 Mutations in the gene encoding hepatocyte nuclear factor-4alpha (HNF-4alpha) result in maturity-onset diabetes of the young (MODY). To determine the contribution of HNF-4alpha to the maintenance of glucose homeostasis by the beta cell in vivo, we derived a ... Full text Link to item Cite

HNF-4alpha: from MODY to late-onset type 2 diabetes.

Journal Article Trends Mol Med · November 2004 Maturity-onset diabetes of the young (MODY) is a rare subtype of type 2 diabetes that is characterized by autosomal-dominant inheritance and can be caused by mutations in hepatocyte nuclear factor 4alpha (HNF-4alpha). Odom and colleagues have combined chro ... Full text Link to item Cite