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R L Atkinson

Bio: R L Atkinson is an academic researcher. The author has contributed to research in topics: White adipose tissue & Adipose tissue. The author has an hindex of 1, co-authored 1 publications receiving 3346 citations.

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Journal ArticleDOI
TL;DR: A role for the abnormal regulation of this cytokine in the pathogenesis of obesity-related insulin resistance is suggested as well as the effects of weight reduction by dietary treatment of obesity on the adipose expression of TNF-alpha mRNA.
Abstract: Obesity is frequently associated with insulin resistance and abnormal glucose homeostasis. Recent studies in animal models have indicated that TNF-alpha plays an important role in mediating the insulin resistance of obesity through its overexpression in fat tissue. However, the mechanisms linking obesity to insulin resistance and diabetes in humans remain largely unknown. In this study we examined the expression pattern of TNF-alpha mRNA in adipose tissues from 18 control and 19 obese premenopausal women by Northern blot analysis. TNF-alpha protein concentrations in plasma and in conditioned medium of explanted adipose tissue were measured by ELISA. Furthermore, the effects of weight reduction by dietary treatment of obesity on the adipose expression of TNF-alpha mRNA were also analyzed in nine premenopausal obese women, before and after a controlled weight-reduction program. These studies demonstrated that obese individuals express 2.5-fold more TNF-alpha mRNA in fat tissue relative to the lean controls (P < 0.001). Similar increases were also observed in adipose production of TNF-alpha protein but circulating TNF-alpha levels were extremely low or undetectable. A strong positive correlation was observed between TNF-alpha mRNA expression levels in fat tissue and the level of hyperinsulinemia (P < 0.001), an indirect measure of insulin resistance. Finally, body weight reduction in obese subjects which resulted in improved insulin sensitivity was also associated with a decrease in TNF-alpha mRNA expression (45%, P < 0.001) in fat tissue. These results suggest a role for the abnormal regulation of this cytokine in the pathogenesis of obesity-related insulin resistance.

3,499 citations


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Journal ArticleDOI
14 Dec 2006-Nature
TL;DR: Dysfunction of the immune response and metabolic regulation interface can be viewed as a central homeostatic mechanism, dysfunction of which can lead to a cluster of chronic metabolic disorders, particularly obesity, type 2 diabetes and cardiovascular disease.
Abstract: Metabolic and immune systems are among the most fundamental requirements for survival. Many metabolic and immune response pathways or nutrient- and pathogen-sensing systems have been evolutionarily conserved throughout species. As a result, immune response and metabolic regulation are highly integrated and the proper function of each is dependent on the other. This interface can be viewed as a central homeostatic mechanism, dysfunction of which can lead to a cluster of chronic metabolic disorders, particularly obesity, type 2 diabetes and cardiovascular disease. Collectively, these diseases constitute the greatest current threat to global human health and welfare.

7,536 citations

Journal ArticleDOI
TL;DR: The pathophysiology seems to be largely attributable to insulin resistance with excessive flux of fatty acids implicated, and a proinflammatory state probably contributes to the metabolic syndrome.

5,810 citations

Journal ArticleDOI
18 Jul 2001-JAMA
TL;DR: Elevated levels of CRP and IL-6 predict the development of type 2 DM, and data support a possible role for inflammation in diabetogenesis.
Abstract: Results Baseline levels of IL-6 (P,001) and CRP (P,001) were significantly higher among cases than among controls The relative risks of future DM for women in the highest vs lowest quartile of these inflammatory markers were 75 for IL-6 (95% confidence interval [CI], 37-154) and 157 for CRP (95% CI, 65-379) Positive associations persisted after adjustment for body mass index, family history of diabetes, smoking, exercise, use of alcohol, and hormone replacement therapy; multivariate relative risks for the highest vs lowest quartiles were 23 for IL-6 (95% CI, 09-56; P for trend=07) and 42 for CRP (95% CI, 15-120; P for trend=001) Similar results were observed in analyses limited to women with a baseline hemoglobin A1c of 60% or less and after adjustment for fasting insulin level

4,107 citations

Journal ArticleDOI
TL;DR: The molecular and cellular underpinnings of obesity-induced inflammation and the signaling pathways at the intersection of metabolism and inflammation that contribute to diabetes are discussed.
Abstract: Over the last decade, an abundance of evidence has emerged demonstrating a close link between metabolism and immunity. It is now clear that obesity is associated with a state of chronic low-level inflammation. In this article, we discuss the molecular and cellular underpinnings of obesity-induced inflammation and the signaling pathways at the intersection of metabolism and inflammation that contribute to diabetes. We also consider mechanisms through which the inflammatory response may be initiated and discuss the reasons for the inflammatory response in obesity. We put forth for consideration some hypotheses regarding important unanswered questions in the field and suggest a model for the integration of inflammatory and metabolic pathways in metabolic disease.

3,913 citations

Journal ArticleDOI
TL;DR: The discovery that obesity itself results in an inflammatory state in metabolic tissues ushered in a research field that examines the inflammatory mechanisms in obesity, and metaflammation is summarized, defined as low-grade, chronic inflammation orchestrated by metabolic cells in response to excess nutrients and energy.
Abstract: The modern rise in obesity and its strong association with insulin resistance and type 2 diabetes have elicited interest in the underlying mechanisms of these pathologies. The discovery that obesity itself results in an inflammatory state in metabolic tissues ushered in a research field that examines the inflammatory mechanisms in obesity. Here, we summarize the unique features of this metabolic inflammatory state, termed metaflammation and defined as low-grade, chronic inflammation orchestrated by metabolic cells in response to excess nutrients and energy. We explore the effects of such inflammation in metabolic tissues including adipose, liver, muscle, pancreas, and brain and its contribution to insulin resistance and metabolic dysfunction. Another area in which many unknowns still exist is the origin or mechanism of initiation of inflammatory signaling in obesity. We discuss signals or triggers to the inflammatory response, including the possibility of endoplasmic reticulum stress as an important contributor to metaflammation. Finally, we examine anti-inflammatory therapies for their potential in the treatment of obesity-related insulin resistance and glucose intolerance.

3,045 citations