Match!

Central Role of the Adipocyte in the Metabolic Syndrome

Published on Jan 1, 2001in Journal of Investigative Medicine1.994
· DOI :10.2310/6650.2001.34108
Richard N. Bergman96
Estimated H-index: 96
(SC: University of Southern California),
Gregg W. Van Citters8
Estimated H-index: 8
(SC: University of Southern California)
+ 4 AuthorsMartin Ellmerer4
Estimated H-index: 4
(SC: 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 (178)
📖 Papers frequently viewed together
6,270 Citations
797 Citations
200143.07Nature
3,676 Citations
78% of Scinapse members use related papers. After signing in, all features are FREE.
References29
Newest
117 Citations
#1Melvin K. DeaH-Index: 9
#2G W Van CittersH-Index: 2
Last. Richard N. BergmanH-Index: 96
view all 6 authors...
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 CitationsSource
#1Steven D. Mittelman (SC: University of Southern California)H-Index: 30
#2Richard N. Bergman (SC: University of Southern California)H-Index: 96
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...
72 CitationsSource
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 CitationsSource
#1Melania Manco (CUA: The Catholic University of America)H-Index: 44
#2Av Greco (CUA: The Catholic University of America)H-Index: 38
Last. Giovanni Gasbarrini (CUA: The Catholic University of America)H-Index: 87
view all 6 authors...
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...
144 CitationsSource
#1Hean ZhuangH-Index: 4
#2Arin BhattacharjeeH-Index: 22
Last. Ming LiH-Index: 24
view all 9 authors...
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 CitationsSource
#1Marianthe Hamilton-Wessler (SC: University of Southern California)H-Index: 11
#2Marilyn Ader (SC: University of Southern California)H-Index: 28
Last. Richard N. Bergman (SC: University of Southern California)H-Index: 96
view all 7 authors...
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 ...
70 CitationsSource
#1Zengkui GuoH-Index: 1
#2Donald D. Hensrud (Mayo Clinic)H-Index: 28
Last. Michael Dennis JensenH-Index: 8
view all 4 authors...
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...
183 CitationsSource
#1J. D. McGarry (UTSW: University of Texas Southwestern Medical Center)H-Index: 2
#2R. L. Dobbins (UTSW: University of Texas Southwestern Medical Center)H-Index: 1
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...
496 CitationsSource
#1Neil B. RudermanH-Index: 91
#2Donald J. ChisholmH-Index: 62
Last. Stephen H. SchneiderH-Index: 30
view all 4 authors...
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...
692 CitationsSource
Cited By178
Newest
#1Zeinab Nouri (Kermanshah University of Medical Sciences)
#2Marziyeh Hajialyani (Kermanshah University of Medical Sciences)H-Index: 4
Last. Mohammad Abdollahi (Tehran University of Medical Sciences)H-Index: 69
view all 6 authors...
Metabolic syndrome (MetS) includes a series of metabolic abnormalities that leads to diabetes mellitus and cardiovascular diseases. Plant extracts, due to their unique advantages like anti-inflammatory, antioxidant, and insulin sensitizing properties, are interesting therapeutic options to manage MetS; however, the poor solubility and low bioavailability of lipophilic bioactive components in the herbal extracts are two critical challenges. Nano-scale delivery systems are suitable to improve deli...
Source
#1Zahra Yari (Shahid Beheshti University of Medical Sciences and Health Services)H-Index: 5
#2Mina Movahedian (Shahid Beheshti University of Medical Sciences and Health Services)
Last. Azita Hekmatdoost (Shahid Beheshti University of Medical Sciences and Health Services)H-Index: 22
view all 6 authors...
Purpose Hesperidin as an antioxidant flavonoid exerts anti-adipogenic, anti-inflammatory, anti-oxidant and anti-hypercholesterolemic effects. Besides, the increasing prevalence of metabolic syndrome (MetS) and its allied complications, on the one hand, and the willingness of individuals to use natural products for curing their diseases, on the other hand, led to the design of this study to evaluate the efficacy of hesperidin in normalizing the metabolic abnormalities in patients with MetS.
Source
#1Zhe Wu (PKU: Peking University)H-Index: 2
#2Jun Xu (PKU: Peking University)H-Index: 2
Last. Yulan Liu (PKU: Peking University)H-Index: 6
view all 10 authors...
2 CitationsSource
#1Hui Chen (UTS: University of Technology, Sydney)H-Index: 24
#2Jane P. M. Ng (UTS: University of Technology, Sydney)H-Index: 1
Last. Stella M. Valenzuela (UTS: University of Technology, Sydney)H-Index: 28
view all 5 authors...
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...
Source
#1Zhe Wu (PKU: Peking University)H-Index: 2
#2Jiang Tan (PKU: Peking University)H-Index: 2
Last. Yulan Liu (PKU: Peking University)H-Index: 6
view all 9 authors...
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 ...
2 CitationsSource
#1Jay I. Lakkis (U.H.: University of Hawaii at Manoa)H-Index: 2
#2Mathew R. Weir (UMB: University of Maryland, Baltimore)H-Index: 1
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...
5 CitationsSource
#1Stephan Wueest (Boston Children's Hospital)H-Index: 15
#2Céline I. Laesser (Boston Children's Hospital)H-Index: 1
Last. Daniel Konrad (UZH: University of Zurich)H-Index: 24
view all 9 authors...
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...
10 CitationsSource
#1Katarzyna Kaczmarczyk (Józef Piłsudski University of Physical Education in Warsaw)H-Index: 5
#2Aleksandra Pituch-Zdanowska (Medical University of Warsaw)H-Index: 2
Last. Aleksander Ronikier (Józef Piłsudski University of Physical Education in Warsaw)H-Index: 1
view all 5 authors...
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 CitationsSource
#2Varshil Mehta (M.G.M. Medical College)H-Index: 12
Last. James H. O'KeefeH-Index: 37
view all 4 authors...
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...
7 CitationsSource
#1Guihovany Alberto García Casilimas (Universidad de La Sabana)H-Index: 1
#2Daniel Augusto Martin (Universidad de La Sabana)H-Index: 1
Last. Andrés Felipe Barragán (Universidad de La Sabana)H-Index: 1
view all 6 authors...
1 CitationsSource