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Obesity is a medical condition, sometimes considered a disease, in which excess body fat has accumulated to such an extent that it may negatively affect health. People are classified as obese when their body mass index (BMI)—a person's weight divided by the square of the person's height—is over 30 kg/m2; the range 25–30 kg/m2 is defined as overweight. Some East Asian countries use lower values to calculate obesity. Obesity is a major cause of disability and is correlated with various diseases and conditions, particularly cardiovascular diseases, type 2 diabetes, obstructive sleep apnea, certain types of cancer, and osteoarthritis.
Leptin is a hormone predominantly made by adipose cells and its primary role is likely to regulate long-term energy balance.
Adipose tissue, body fat, or simply fat is a loose connective tissue composed mostly of adipocytes. In addition to adipocytes, adipose tissue contains the stromal vascular fraction (SVF) of cells including preadipocytes, fibroblasts, vascular endothelial cells and a variety of immune cells such as adipose tissue macrophages. Adipose tissue is derived from preadipocytes. Its main role is to store energy in the form of lipids, although it also cushions and insulates the body. Far from being hormonally inert, adipose tissue has, in recent years, been recognized as a major endocrine organ, as it produces hormones such as leptin, estrogen, resistin, and cytokines. In obesity, adipose tissue is also implicated in the chronic release of pro-inflammatory markers known as adipokines, which are responsible for the development of metabolic syndrome, a constellation of diseases including, but not limited to, type 2 diabetes, cardiovascular disease and atherosclerosis. The two types of adipose tissue are white adipose tissue (WAT), which stores energy, and brown adipose tissue (BAT), which generates body heat. The formation of adipose tissue appears to be controlled in part by the adipose gene. Adipose tissue – more specifically brown adipose tissue – was first identified by the Swiss naturalist Conrad Gessner in 1551.
Adiponectin is a protein hormone and adipokine, which is involved in regulating glucose levels as well as fatty acid breakdown. In humans it is encoded by the ADIPOQ gene and it is produced primarily in adipose tissue, but also in muscle, and even in the brain.
Fat mass and obesity-associated protein also known as alpha-ketoglutarate-dependent dioxygenase FTO is an enzyme that in humans is encoded by the FTO gene located on chromosome 16. As one homolog in the AlkB family proteins, it is the first mRNA demethylase that has been identified. Certain alleles of the FTO gene appear to be correlated with obesity in humans.
Carboxypeptidase E (CPE), also known as carboxypeptidase H (CPH) and enkephalin convertase, is an enzyme that in humans is encoded by the CPE gene. This enzyme catalyzes the release of C-terminal arginine or lysine residues from polypeptides.
Niemann-Pick disease, type C1 (NPC1) is a disease of a membrane protein that mediates intracellular cholesterol trafficking in mammals. In humans the protein is encoded by the NPC1 gene.
The sodium/glucose cotransporter 2 (SGLT2) is a protein that in humans is encoded by the SLC5A2 gene.
Melanocortin 4 receptor (MC4R) is a melanocortin receptor that in humans is encoded by the MC4R gene. It encodes the MC4R protein, a G protein-coupled receptor (GPCR) that binds α-melanocyte stimulating hormone (α-MSH). In mouse models, MC4 receptors have been found to be involved in feeding behaviour, the regulation of metabolism, sexual behaviour, and male erectile function.
Leptin receptor, also known as LEP-R or OB-R, is a type I cytokine receptor, a protein that in humans is encoded by the LEPR gene. LEP-R functions as a receptor for the fat cell-specific hormone leptin. LEP-R has also been designated as CD295. Its location is the cell membrane, and it has extracellular, trans-membrane and intracellular sections.
Monocarboxylate transporter 8 (MCT8) is an active transporter protein that in humans is encoded by the SLC16A2 gene.
RPGRIP1L is a human gene.
Like many other medical conditions, obesity is the result of an interplay between environmental and genetic factors. Studies have identified variants in several genes that may contribute to weight gain and body fat distribution; although, only in a few cases are genes the primary cause of obesity.
N6-Methyladenosine (m6A) was originally identified and partially characterised in the 1970s, and is an abundant modification in mRNA and DNA. It is found within some viruses, and most eukaryotes including mammals, insects, plants and yeast. It is also found in tRNA, rRNA, and small nuclear RNA (snRNA) as well as several long non-coding RNA, such as Xist.
Lysophospholipase-like 1 is a protein in humans that is encoded by the LYPLAL1 gene. The protein is a α/β-hydrolase of uncharacterized metabolic function. Genome-wide association studies in humans have linked the gene to fat distribution and waist-to-hip ratio. The protein's enzymatic function is unclear. LYPLAL1 was reported to act as a triglyceride lipase in adipose tissue and another study suggested that the protein may play a role in the depalmitoylation of calcium-activated potassium channels. However, LYPLAL1 does not depalmitoylate the oncogene Ras and a structural and enzymatic study concluded that LYPLAL1 is generally unable to act as a lipase and is instead an esterase that prefers short-chain substrates, such as acetyl groups. Structural comparisons have suggested that LYPLAL1 might be a protein deacetylase, but this has not been experimentally tested.
Rudolph Leibel is the Christopher J. Murphy Professor of Diabetes Research, Professor of Pediatrics and Medicine at Columbia University Medical Center, and Director of the Division of Molecular Genetics in the Department of Pediatrics. He is also Co-Director of the Naomi Berrie Diabetes Center and Executive Director of the Russell and Angelica Berrie Program in Cellular Therapy, Co-Director of the New York Obesity Research Center and the Columbia University Diabetes and Endocrinology Research Center.
MeRIPseq stands for methylated RNA immunoprecipitation sequencing, which is a method for detection of post-transcriptional RNA modifications. It is also called m6A-seq.
Ismaa Sadaf Farooqi is a Wellcome Trust Senior Research fellow in Clinical Science, professor of Metabolism and Medicine at the University of Cambridge and a consultant physician at Addenbrooke's Hospital in Cambridge, UK.
Magdalena Skipper is a British geneticist and the editor-in-chief of the journal Nature. She previously served as an editor of Nature Reviews Genetics and the open access journal Nature Communications.
Eleftheria Maratos-Flier is an American endocrinologist, and emerita Professor of Medicine at Harvard Medical School, best known for her expertise in the pathophysiology and prevention of obesity-related metabolic disorders, and for her discoveries on the neuroendocrine control of feeding behaviour. She is a contributing author to known textbooks and reviews in internal medicine, endocrinology, and physiology. Her marriage with professor Jeffrey Flier, was noted by Forbes as a lasting and productive bond between eminent medical scholars. They have two adult daughters who are also physicians. She is also known as Terry Maratos-Flier.
References
- 1 2 3 4 "About the Editors | Nature Reviews Genetics". www.nature.com. Retrieved 2022-04-03.
- ↑ Meyer, Kate D.; Saletore, Yogesh; Zumbo, Paul; Elemento, Olivier; Mason, Christopher E.; Jaffrey, Samie R. (2012-06-22). "Comprehensive Analysis of mRNA Methylation Reveals Enrichment in 3′ UTRs and near Stop Codons". Cell. 149 (7): 1635–1646. doi:10.1016/j.cell.2012.05.003. ISSN 0092-8674. PMC 3383396 . PMID 22608085.
- ↑ Blüher, Matthias (2019). "Obesity: global epidemiology and pathogenesis". Nature Reviews Endocrinology. 15 (5): 288–298. doi:10.1038/s41574-019-0176-8. ISSN 1759-5037. PMID 30814686. S2CID 71146382.
- ↑ Welle (www.dw.com), Deutsche. "Germans in UK navigate difficult plans amid further Brexit uncertainty | DW | 09.11.2020". DW.COM. Retrieved 2022-04-03.
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