Hexosamines regulate leptin production in human subcutaneous adipocytes.

@article{Considine2000HexosaminesRL,
  title={Hexosamines regulate leptin production in human subcutaneous adipocytes.},
  author={Robert Vincent Considine and Robert C. Cooksey and Lloyd B. Williams and R L Fawcett and P Zhang and Walter T. Ambrosius and Rebekah Whitfield and Rosemarie Jones and M. Inman and John Huse and Donald A. McClain},
  journal={The Journal of clinical endocrinology and metabolism},
  year={2000},
  volume={85 10},
  pages={
          3551-6
        }
}
The hexosamine biosynthetic pathway has recently been proposed as a mechanism through which cells "sense" nutrient flux to regulate leptin release. This study was undertaken to examine the regulation of leptin production by hexosamines in human adipocytes. Adipose tissue UDP-N-acetylglucosamine, an end product of hexosamine biosynthesis, was elevated 3.2-fold, and ob messenger ribonucleic acid was elevated 2-fold in the sc adipose tissue of 17 obese [body mass index (BMI), 41.3+/-12.0 kg/m2… Expand
Role of hexosamines in insulin resistance and nutrient sensing in human adipose and muscle tissue.
TLDR
The hypothesis that the hexosamine pathway in adipose tissue, not in muscle, is a FFA-sensing pathway and could be involved in the regulation of leptin expression is supported. Expand
Hexosamines regulate leptin production in 3T3-L1 adipocytes through transcriptional mechanisms.
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It is demonstrated that glucose and hexosamines regulate leptin production through transcriptional mechanisms localized to the proximal portion of the LEP promoter and Hexosamine-mediated regulation of LEP gene expression does not depend on Sp1 binding to traditional sites on the promoter. Expand
Hexosamine flux, the O-GlcNAc modification, and the development of insulin resistance in adipocytes
TLDR
Dynamic and inducible O-GlcNAc modification is emerging as a modulator of insulin sensitivity in adipocytes as a major downstream event consuming and incorporating the final product of the hexosamine biosynthesis pathway. Expand
Hexosamines as mediators of nutrient sensing: relevance to obesity, insulin resistance, and diabetes
TLDR
The results suggest a mechanism by which chronic overnutrition leads to the phenotype of type 2 diabetes, which is regulated by the levels of the end-product of the hexosamine pathway, UDP-N-acetyl glucosamine. Expand
Activation of the hexosamine signaling pathway in adipose tissue results in decreased serum adiponectin and skeletal muscle insulin resistance.
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Increased hexosamine levels in fat, mimicking excess nutrient delivery, are sufficient to cause insulin resistance in skeletal muscle. Expand
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TLDR
The data support that the O-GlcNAc modification is involved in the regulation of adipocytokine secretion upon the induction of insulin resistance in human adipocytes and the classical method of hyperglycemia and hyperinsulinemia. Expand
Acidosis downregulates leptin production from cultured adipocytes through a glucose transport-dependent post-transcriptional mechanism.
TLDR
Dose-response curves for the inhibition of glucose uptake showed that decreasing glucose transport to the same extent as with acid was sufficient to drive down leptin secretion, independently of changes of leptin mRNA. Expand
Glucosamine attenuates increases of intraabdominal fat, serum leptin levels, and insulin resistance induced by a high-fat diet in rats.
TLDR
Glucosamine administration was able to partially or completely inhibit some effects of the HF diet by reducing fat depot weight and serum leptin levels, thus resulting in a smaller increase in the insulinemic response to a glucose injection and lower postabsorptive glycemia. Expand
Transgenic Mice Overexpressing the Rate‐Limiting Enzyme for Hexosamine Synthesis in Skeletal Muscle or Adipose Tissue Exhibit Total Body Insulin Resistance
TLDR
Excess hexosamine flux leads to a coordinated response whereby fuel is shunted toward long‐term storage, mirroring the “thrifty phenotype”, suggesting a mechanism by which chronic overnutrition leads to the phenotype of type 2 diabetes. Expand
Regulation of Leptin Production
  • R. Considine
  • Biology, Medicine
  • Reviews in Endocrine and Metabolic Disorders
  • 2004
TLDR
In addition to adipose tissue, leptin is produced in several other places including placenta, bone marrow, stomach, muscle and perhaps brain, thus increasing the number of potential regulatory roles for this hormone. Expand
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