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Central Role of the Adipocyte in the Metabolic Syndrome

Published on Jan 1, 2001in Journal of Investigative Medicine 2.03
· DOI :10.2310/6650.2001.34108
Richard N. Bergman103
Estimated H-index: 103
(University of Southern California),
Gregg W. Van Citters8
Estimated H-index: 8
(University of Southern California)
+ 4 AuthorsMartin Ellmerer25
Estimated H-index: 25
(University of Southern California)
Abstract
Abstract Insulin resistance is associated with a plethora of chronic illnesses, including Type 2 diabetes, dyslipidemia, clotting dysfunction, and colon cancer. The relationship between obesity and insulin resistance is well established, and an increase in obesity in Western countries is implicated in increased incidence of diabetes and other diseases. Central, or visceral, adiposity has been particularly associated with insulin resistance; however, the mechanisms responsible for this association are unclear. Our laboratory has been studying the physiological mechanisms relating visceral adiposity and insulin resistance. Moderate fat feeding of the dog yields a model reminiscent of the metabolic syndrome, including visceral adiposity, hyperinsulinemia, and insulin resistance. We propose that insulin resistance of the liver derives from a relative increase in the delivery of free fatty acids (FFA) from the omental fat depot to the liver (via the portal vein). Increased delivery results from 1) more stored lipids in omental depot, 2) severe insulin resistance of the central fat depot, and 3) possible regulation of visceral lipolysis by the central nervous system. The significance of portal FFA delivery results from the importance of FFA in the control of liver glucose production. Insulin regulates liver glucose output primarily via control of adipocyte lipolysis. Thus, because FFA regulate the liver, it is expected that visceral adiposity will enhance delivery of FFA to the liver and make the liver relatively insulin resistant. It is of interest how the intact organism compensates for insulin resistance secondary to visceral fat deposition. While part of the compensation is enhanced B-cell sensitivity to glucose, an equally important component is reduced liver insulin clearance, which allows for a greater fraction of B-cell insulin secretion to bypass liver degradation, to enter the systemic circulation, and to result in hyperinsulinemic compensation. The signal(s) resulting in B-cell up-regulation and reduced liver insulin clearance with visceral adiposity is (are) unknown, but it appears that the glucagon-like peptide (GLP-1) hormone plays an important role. The integrated response of the organism to central adiposity is complex, involving several organs and tissue beds. An investigation into the integrated response may help to explain the features of the metabolic syndrome.
  • References (29)
  • Citations (176)
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References29
Newest
Published on Feb 24, 2001in Presse Medicale 0.92
Barbier D1
Estimated H-index: 1
116 Citations
Published on Dec 1, 2000in Diabetes 7.27
Melvin K. Dea9
Estimated H-index: 9
,
G W Van Citters2
Estimated H-index: 2
+ 3 AuthorsRichard N. Bergman103
Estimated H-index: 103
Troglitazone is an antidiabetic agent that improves the ability of adipocytes to store triglycerides by enhancing their insulin sensitivity. Although potent in insulin-resistant states, the effect of troglitazone on lipid and glucose turnover in normal animals has not been assessed. Euglycemic clamps were performed as an insulin dose response in normal mongrel dogs (n = 6). Somatostatin was infused without hormone replacement (zero insulin) for 90 min. Insulin was then either portally replaced (...
5 Citations Source Cite
Steven D. Mittelman29
Estimated H-index: 29
(University of Southern California),
Richard N. Bergman103
Estimated H-index: 103
(University of Southern California)
We have shown that insulin controls endogenous glucose production (EGP) indirectly, via suppression of adipocyte lipolysis. Free fatty acids (FFA) and EGP are suppressed proportionately, and when the decline in FFA is prevented during insulin infusion, suppression of EGP is also prevented. The present study tested the hypothesis that suppression of lipolysis under conditions of constant insulin would yield a suppression of EGP. N 6-cyclohexyladenosine (CHA) was used to selectively suppress adipo...
69 Citations Source Cite
Published on Aug 1, 2000in Journal of Clinical Investigation 13.25
Lisa Getty3
Estimated H-index: 3
,
Antonios E. Panteleon1
Estimated H-index: 1
+ 2 AuthorsRichard N. Bergman103
Estimated H-index: 103
Abnormal fat metabolism plays an important role in the pathogenesis of obesity-related type 2 diabetes mellitus. This study examined whether free fatty acid levels (FFAs), like insulin levels, oscillate rapidly in plasma. Peripheral and portal blood samples from dogs were assayed for FFA, glycerol, glucose, and insulin. FFA and glycerol showed correlated oscillatory profiles, with about 8 pulses/hour. Omental lipolysis was also pulsatile, with about 10 pulses/hour, and insulin levels oscillated ...
44 Citations Source Cite
Published on Feb 1, 2000in Metabolism-clinical and Experimental 5.96
Melania Manco43
Estimated H-index: 43
(The Catholic University of America),
Av Greco42
Estimated H-index: 42
(The Catholic University of America)
+ 3 AuthorsGiovanni Gasbarrini85
Estimated H-index: 85
(The Catholic University of America)
A close relationship between elevated plasma free fatty acid (FFA) levels and insulin resistance is commonly reported in obese subjects. The aim of the present study was to evaluate the role of intramuscular triglyceride (mTG) and FFA levels in insulin sensitivity in 30 nondiabetic normal-weight or obese subjects (18 with body mass index [BMI] = 21.8 ± 3.3 kg/m 2 and 12 with BMI = 34.6 ± 2.7 kg/m 2 ) who underwent minor abdominal surgery. Body composition was estimated by isotopic dilution, subs...
141 Citations Source Cite
Published on Jan 1, 2000in Diabetes 7.27
Hean Zhuang4
Estimated H-index: 4
,
Arin Bhattacharjee22
Estimated H-index: 22
+ 6 AuthorsMing Li23
Estimated H-index: 23
The T-type Ca2+ channel is an important determinant of electrical activity and of Ca2+ influx in rat and human pancreatic beta-cells. We have identified and sequenced a cDNA encoding a T-type Ca2+ channel alpha1-subunit derived from INS-1, the rat insulin-secreting cell line. The sequence of the cDNA indicates a protein composed of 2,288 amino acids that shares 96.3% identity to alpha1G, the neuronal T-type Ca2+ channel subunit. The transmembrane domains of the protein are highly conserved, but ...
42 Citations Source Cite
Published on Oct 1, 1999in Diabetologia 6.02
Marianthe Hamilton-Wessler11
Estimated H-index: 11
(University of Southern California),
Marilyn Ader28
Estimated H-index: 28
(University of Southern California)
+ 4 AuthorsRichard N. Bergman103
Estimated H-index: 103
(University of Southern California)
Aims/hypothesis. The provision of stable, reproducible basal insulin is crucial to diabetes management. This study in dogs examined the metabolic effects and interstitial fluid (ISF) profiles of fatty acid acylated insulin, LysB29-tetradecanoyl, des-(B30) human insulin (NN304). Methods. Euglycaemic clamps were carried out under inhalant anaesthesia during equimolar intravenous infusions (3.6 pmol · min–1· kg–1 for 480 min) of human insulin or NN304 (n = 8 per group). Results. Steady-state total ...
69 Citations Source Cite
Published on Aug 1, 1999in Diabetes 7.27
Zengkui Guo1
Estimated H-index: 1
,
Donald D. Hensrud28
Estimated H-index: 28
(Mayo Clinic)
+ 1 AuthorsMichael Dennis Jensen27
Estimated H-index: 27
To examine if postprandial splanchnic/hepatic free fatty acid (FFA) delivery is increased in upper-body (UB) obesity, and to determine the adipose tissue depots responsible for the greater postprandial FFA availability, we measured systemic and regional uptake and release of FFAs ([1-(14)C]palmitate) before and during a 5-h frequent-feeding mixed meal in eight UB and eight lower-body (LB) obese women. Postabsorptive FFA flux and splanchnic FFA delivery were not different in UB and LB obese women...
179 Citations Source Cite
Published on Jan 21, 1999in Diabetologia 6.02
J. D. McGarry2
Estimated H-index: 2
(University of Texas Southwestern Medical Center),
R. L. Dobbins1
Estimated H-index: 1
(University of Texas Southwestern Medical Center)
tant energy source for most body tissues, particularly during periods of food deprivation, but recent evidence suggests that these same molecules subserve a much broader function in whole body fuel homeostasis by virtue of their ability to act as potent signalling entities in a variety of cellular processes. One such auxiliary role of NEFA is to heighten the responsiveness of the pancreatic beta cell to a variety of insulin secretagogues. Importantly, this fatty acid-beta cell interaction, thoug...
487 Citations Source Cite
Published on May 1, 1998in Diabetes 7.27
Neil B. Ruderman91
Estimated H-index: 91
,
Donald J. Chisholm62
Estimated H-index: 62
+ 1 AuthorsStephen H. Schneider29
Estimated H-index: 29
Nearly 20 years ago, it was suggested that individuals exist who are not obese on the basis of height and weight, but who, like people with overt obesity, are hyperinsulinemic, insulin-resistant, and predisposed to type 2 diabetes, hypertriglyceridemia, and premature coronary heart disease. Since then it has become increasingly clear that such metabolically obese, normal-weight (MONW) individuals are very common in the general population and that they probably represent one end of the spectrum o...
680 Citations Source Cite
Cited By176
Newest
Published on May 1, 2019in Journal of Cellular and Molecular Medicine 4.30
Zhe Wu2
Estimated H-index: 2
(Peking University),
Jun Xu1
Estimated H-index: 1
(Peking University)
+ 7 AuthorsYulan Liu7
Estimated H-index: 7
(Peking University)
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Published on Dec 1, 2018in Journal of Nanobiotechnology 5.29
Hui Chen21
Estimated H-index: 21
(University of Technology, Sydney),
Jane P. M. Ng1
Estimated H-index: 1
(University of Technology, Sydney)
+ 2 AuthorsStella M. Valenzuela26
Estimated H-index: 26
(University of Technology, Sydney)
Background We have previously shown that intraperitoneal injection of gold nanoparticles (AuNPs, 20–30 nm) into mice, decreases high-fat diet (HFD) induced weight gain and glucose intolerance, via suppression of inflammatory responses in both fat and liver tissues. This study investigates whether AuNPs provide similar benefit to mice with pre-existing obesity. Male C57BL/6 mice were fed a HFD for 15 weeks. AuNPs (OB-EAu 0.0785 μg/g/day, OB-LAu 0.785 μg/g/day, OB-HAu7.85 μg/g/day, ip) were admini...
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Zhe Wu2
Estimated H-index: 2
(Peking University),
Jiang Tan (Peking University)+ 6 AuthorsYulan Liu7
Estimated H-index: 7
(Peking University)
The mesenteric adipose tissue (MAT) lies between the gut and liver and plays a critical role in hepatic metabolic diseases. In the present study, we found that the MAT was prone to inflammation in ...
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Published on Jul 1, 2018in Progress in Cardiovascular Diseases 6.75
Jay I. Lakkis2
Estimated H-index: 2
(University of Hawaii at Manoa),
Mathew R. Weir1
Estimated H-index: 1
(University of Maryland, Baltimore)
Abstract Obesity is a systemic disease of the white adipose tissue, which has evolved into a global epidemic. It is associated with a plethora of adipocyte hormonal (adipokine) imbalances, dysregulation of the energy-balance system, imbalances in metabolic homeostasis, a pro-inflammatory state and multiple target organ damages. Clinically, the obesity phenotype is not homogenous and is more likely to represent a spectrum with varying degrees of metabolic un-health; metabolically-unhealthy obesit...
2 Citations Source Cite
Published on Jan 1, 2018in Diabetes 7.27
Stephan Wueest15
Estimated H-index: 15
(Boston Children's Hospital),
Céline I. Laesser1
Estimated H-index: 1
(Boston Children's Hospital)
+ 6 AuthorsDaniel Konrad27
Estimated H-index: 27
(University of Zurich)
We recently showed that interleukin (IL)-6-type cytokine signaling in adipocytes induces free fatty acid release from visceral adipocytes, thereby promoting obesity-induced hepatic insulin resistance and steatosis. In addition, IL-6-type cytokines may increase the release of leptin from adipocytes and by those means induce glucagon-like peptide 1 (GLP-1) secretion. We thus hypothesized that IL-6-type cytokine signaling in adipocytes may regulate insulin secretion. To this end, mice with adipocyt...
7 Citations Source Cite
Published on Jan 1, 2018in Journal of International Medical Research 1.02
Katarzyna Kaczmarczyk3
Estimated H-index: 3
(Józef Piłsudski University of Physical Education in Warsaw),
Aleksandra Pituch-Zdanowska2
Estimated H-index: 2
(Medical University of Warsaw)
+ 2 AuthorsAleksander Ronikier1
Estimated H-index: 1
(Józef Piłsudski University of Physical Education in Warsaw)
ObjectivesTo evaluate the long-term consequences of preterm birth on anthropometric parameters in women in adolescence and into adulthood.MethodsSeventy girls born preterm (age 12.22 ± 1.52 years) and 48 born at term participated in the first stage. Eighteen years later, 13 of the same women participated in a follow-up and were compared with a control group of 27 women. We compared anthropometric results across the two examinations, and in the second stage, also assessed body composition using b...
1 Citations Source Cite
Published on Dec 1, 2017in Progress in Cardiovascular Diseases 6.75
James J. DiNicolantonio24
Estimated H-index: 24
,
Varshil Mehta8
Estimated H-index: 8
(M.G.M. Medical College)
+ 1 AuthorsJames H. O'Keefe52
Estimated H-index: 52
Abstract Traditionally, the leading hypothesis regarding the development of obesity involves caloric imbalance, whereby the amount of calories consumed exceeds the amount of calories burned which causes obesity. Another hypothesis for why we get fat has surfaced in the last decade which is the idea that the overconsumption of added sugars and refined carbohydrates induce insulin resistance and high insulin levels causing obesity. While insulin is a fat-storing hormone, this hypothesis does not e...
3 Citations Source Cite
Published on Oct 1, 2017in Revista Portuguesa De Pneumologia 1.73
Guihovany Alberto García Casilimas1
Estimated H-index: 1
(Universidad de La Sabana),
Martin Da1
Estimated H-index: 1
(Universidad de La Sabana)
+ 3 AuthorsAndrés Felipe Barragán1
Estimated H-index: 1
(Universidad de La Sabana)
1 Citations Source Cite
José Esteban Costa Gil , Eduardo Spinedi (Facultad de Ciencias Médicas)
Resumen En esta parte de la revision se describe la relacion funcional entre el metabolismo de los lipidos y los hidratos de carbono y su interdependencia, desde el ciclo glucosa-acido grasos y la hipotesis portal de la insulinorresistencia a los nuevos conocimientos sobre los adipocitos marrones y beiges, con enfasis en el normal funcionamiento de un patron endocrino cuya disfuncion es clave en la fisiopatologia de la DMT2 y la obesidad. Se discute la ectopia o el asiento de grasa en el tejido ...
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Published on Jan 1, 2017in American Journal of Infection Control 1.93
Judyta Nowak4
Estimated H-index: 4
(University of Wrocław),
Barbara Borkowska5
Estimated H-index: 5
(University of Wrocław),
Bogusław Pawłowski21
Estimated H-index: 21
(University of Wrocław)
Background Male gender and adiposity are considered to be risk factors for Staphylococcus aureus carriage. We tested whether colonization is related to free testosterone (fT) level and adiposity, measured with body mass index (BMI) and body fat percentage (BFP), in healthy adults. Methods Blood sample and throat swabs were taken twice (at 4-week intervals) from healthy men and women aged 18-36 years. fT level, height, weight, and BFP were measured. Participants were classified as persistent carr...
1 Citations Source Cite