Hormone Resistance in Diabetes and Obesity: Insulin, Leptin, and
FGF21

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

Abstract

This an edited transcript of the Lee E. Farr Lecture given by Dr. Jeffrey Flier on May 8, 2012, at the culmination of the annual Student Research Day at the Yale School of Medicine. In this presentation, Dr. Flier discusses his and his wife’s research on insulin, leptin, and FGF21 in the context of his reflections upon his life’s work and his advice for young investigators.

Related collections

Most cited references 7

Record: found
Abstract: found
Article: not found

A high-fat, ketogenic diet induces a unique metabolic state in mice.

Fen Liu, Eleftheria Maratos-Flier, Ian R. Kennedy … (2007)

Ketogenic diets have been used as an approach to weight loss on the basis of the theoretical advantage of a low-carbohydrate, high-fat diet. To evaluate the physiological and metabolic effects of such diets on weight we studied mice consuming a very-low-carbohydrate, ketogenic diet (KD). This diet had profound effects on energy balance and gene expression. C57BL/6 mice animals were fed one of four diets: KD; a commonly used obesogenic high-fat, high-sucrose diet (HF); 66% caloric restriction (CR); and control chow (C). Mice on KD ate the same calories as mice on C and HF, but weight dropped and stabilized at 85% initial weight, similar to CR. This was consistent with increased energy expenditure seen in animals fed KD vs. those on C and CR. Microarray analysis of liver showed a unique pattern of gene expression in KD, with increased expression of genes in fatty acid oxidation pathways and reduction in lipid synthesis pathways. Animals made obese on HF and transitioned to KD lost all excess body weight, improved glucose tolerance, and increased energy expenditure. Analysis of key genes showed similar changes as those seen in lean animals placed directly on KD. Additionally, AMP kinase activity was increased, with a corresponding decrease in ACC activity. These data indicate that KD induces a unique metabolic state congruous with weight loss.

0 comments Cited 171 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

The syndromes of insulin resistance and acanthosis nigricans. Insulin-receptor disorders in man.

P. Gorden, Cara M. Martin, Stephen Archer … (1976)

In six patients with acanthosis nigricans variable degrees of glucose intolerance, hyperinsulinemia and marked resistance to exogenous insulin were found. Studies of insulin receptors on circulating monocytes suggest that the insulin resistance in these patients was due to a marked decrease in insulin binding to its membrane receptors. When these patients were fasted, there was a fall in plasma insulin but no increase in insulin binding, suggesting that the receptor defect was not secondary to the hyperinsulinemia. The clinical features shared by these cases and several similar ones previously reported may be divided into two unique clinical syndromes: Type A, a syndrome in younger females with signs of virilization or accelerated growth, in whom the receptor defect may be primary, and Type B, a syndrome in older females with signs of an immunologic disease, in whom circulating antibodies to the insulin receptor are found.

0 comments Cited 95 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Severely impaired adipsin expression in genetic and acquired obesity.

J Flier, K S Cook, P Usher … (1987)

Adipsin, a serine protease homolog, is synthesized and secreted by adipose cells and is found in the bloodstream. The expression of adipsin messenger RNA (mRNA) and protein was analyzed in rodents during metabolic perturbations and in several experimental models of obesity. Adipsin mRNA abundance is increased in adipose tissue during fasting in normal rats and in diabetes due to streptozotocin-induced insulin deficiency. Adipsin mRNA abundance decreased during the continuous infusion of glucose, which induces a hyperglycemic, hyperinsulinemic state that is accompanied by an increased adipose mass; it is suppressed (greater than 100-fold) in two strains of genetically obese mice (db/db and ob/ob), compared to their congenic counterparts, and is also reduced when obesity is induced chemically by injection of monosodium glutamate into newborn mice. Circulating adipsin protein is decreased in these animal models of obesity, as determined by immunoblotting with antisera to adipsin. Little change in adipsin expression is observed in a model of obesity obtained by pure overfeeding of normal rats (cafeteria model). These data suggest a possible role for adipsin in the above-mentioned disordered metabolic states, and raise the possibility that adipsin expression may be used to distinguish obesities that arise from certain genetic or metabolic defects from those that result from pure overfeeding.

0 comments Cited 62 times – based on 0 reviews      Review now

Bookmark

All references

Author and article information

Journal

Journal ID (nlm-ta): Yale J Biol Med

Journal ID (iso-abbrev): Yale J Biol Med

Journal ID (pmc): yjbm

Journal ID (publisher-id): YJBM

Title: The Yale Journal of Biology and Medicine

Publisher: YJBM

ISSN (Print): 0044-0086

ISSN (Electronic): 1551-4056

Publication date (Electronic): 25 September 2012

Publication date Collection: September 2012

Volume: 85

Issue: 3

Pages: 405-414

Affiliations

Dean of the Faculty of Medicine, Harvard University, Harvard Medical School, Boston, Massachusetts

Author notes

To whom all correspondence should be addressed: Jeffrey S. Flier, MD, Dean of the Faculty of Medicine, Harvard University, Harvard Medical School, 25 Shattuck St. – Gordon Hall, Room 111, Boston, MA 02115; Email: Jeffrey_Flier@ 123456hms.harvard.edu .

Article

Publisher ID: yjbm853405

PMC ID: 3447204

PubMed ID: 23012588

SO-VID: 8de51acd-4ca3-4208-ba0e-3a07aed3c986

License:

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License, which permits for noncommercial use, distribution, and reproduction in any digital medium, provided the original work is properly cited and is not altered in any way.

Hormone Resistance in Diabetes and Obesity: Insulin, Leptin, and FGF21

Read this article at

Abstract

Related collections

GLUT4 biology

Most cited references 7

A high-fat, ketogenic diet induces a unique metabolic state in mice.

The syndromes of insulin resistance and acanthosis nigricans. Insulin-receptor disorders in man.

Severely impaired adipsin expression in genetic and acquired obesity.

Author and article information

Journal

Affiliations

Author notes

Article

History

Categories

Comments

Comment on this article

Similar content 26

Cited by 7

Most referenced authors 389