Adipose tissue Adipose tissue (also known as body fat or simply fat) is a loose connective tissue composed mostly of adipocytes. It also contains the stromal vascular fraction (SVF) of cells including preadipocytes, fibroblasts, Blood vessel, vascular endothel ...

is an

endocrine The endocrine system is a messenger system in an organism comprising feedback loops of hormones that are released by internal glands directly into the circulatory system and that target and regulate distant organs. In vertebrates, the hypotha ...

organ that secretes numerous protein

hormones A hormone (from the Greek participle , "setting in motion") is a class of signaling molecules in multicellular organisms that are sent to distant organs or tissues by complex biological processes to regulate physiology and behavior. Hormones a ...

, including

leptin Leptin (from Ancient Greek, Greek λεπτός ''leptos'', "thin" or "light" or "small"), also known as obese protein, is a protein hormone predominantly made by adipocytes (cells of adipose tissue). Its primary role is likely to regulate long ...

, adiponectin, and

resistin Resistin, also known as adipose tissue-specific secretory factor (ADSF) or C/EBP-epsilon-regulated myeloid-specific secreted cysteine-rich protein (XCP1), is a cysteine-rich peptide hormone that is derived from adipose tissue and, in humans, is ...

. These hormones generally influence

energy metabolism Bioenergetics is a field in biochemistry and cell biology that concerns energy flow through living systems. This is an active area of biological research that includes the study of the transformation of energy in living organisms and the study ...

, which is of great interest to the understanding and treatment of

type 2 diabetes Type 2 diabetes (T2D), formerly known as adult-onset diabetes, is a form of diabetes mellitus that is characterized by high blood sugar, insulin resistance, and relative lack of insulin. Common symptoms include increased thirst, frequent ...

and

obesity Obesity is a medical condition, considered by multiple organizations to be a disease, in which excess Adipose tissue, body fat has accumulated to such an extent that it can potentially have negative effects on health. People are classifi ...

. Their relative roles in modifying

appetite Appetite is the desire to eat food items, usually due to hunger. Appealing foods can stimulate appetite even when hunger is absent, although appetite can be greatly reduced by satiety. Appetite exists in all higher life-forms, and serves to reg ...

, insulin resistance and

atherosclerosis Atherosclerosis is a pattern of the disease arteriosclerosis, characterized by development of abnormalities called lesions in walls of arteries. This is a chronic inflammatory disease involving many different cell types and is driven by eleva ...

are the subjects of intense research, as they may be modifiable causes of morbidity in people with obesity.

History of adipose-derived hormones

It had been shown that adipose tissue secreted some unknown factor that influenced appetite. However, the importance of adipose tissue as an endocrine organ was only fully appreciated in 1995 with the discovery of leptin, the protein product of the Ob gene. Leptin is a strong appetite suppressant that, when depleted, causes early onset severe obesity in humans and in

animal model An animal model (short for animal disease model) is a living, non-human, often genetic-engineered animal used during the research and investigation of human disease, for the purpose of better understanding the disease process without the risk of ha ...

s. Low levels of

in the

blood plasma Blood plasma is a light Amber (color), amber-colored liquid component of blood in which blood cells are absent, but which contains Blood protein, proteins and other constituents of whole blood in Suspension (chemistry), suspension. It makes up ...

have been heavily associated with people who have moderate to severe forms of depression.

Leptin Leptin (from Ancient Greek, Greek λεπτός ''leptos'', "thin" or "light" or "small"), also known as obese protein, is a protein hormone predominantly made by adipocytes (cells of adipose tissue). Its primary role is likely to regulate long ...

is known to influence moods and

cognition Cognition is the "mental action or process of acquiring knowledge and understanding through thought, experience, and the senses". It encompasses all aspects of intellectual functions and processes such as: perception, attention, thought, ...

by inducing some structural and functional changes within the

hippocampus The hippocampus (: hippocampi; via Latin from Ancient Greek, Greek , 'seahorse'), also hippocampus proper, is a major component of the brain of humans and many other vertebrates. In the human brain the hippocampus, the dentate gyrus, and the ...

and

prefrontal cortex In mammalian brain anatomy, the prefrontal cortex (PFC) covers the front part of the frontal lobe of the cerebral cortex. It is the association cortex in the frontal lobe. The PFC contains the Brodmann areas BA8, BA9, BA10, BA11, BA12, ...

. Also, leptin has been shown to activate

signal transduction pathways Signal transduction is the process by which a chemical or physical signal is transmitted through a cell as a series of molecular events. Proteins responsible for detecting stimuli are generally termed receptors, although in some cases the term ...

associated with

dopamine Dopamine (DA, a contraction of 3,4-dihydroxyphenethylamine) is a neuromodulatory molecule that plays several important roles in cells. It is an organic chemical of the catecholamine and phenethylamine families. It is an amine synthesized ...

and mTOR, which can increase synaptogenesis.

's role in

neuroplasticity Neuroplasticity, also known as neural plasticity or just plasticity, is the ability of neural networks in the brain to change through neurogenesis, growth and reorganization. Neuroplasticity refers to the brain's ability to reorganize and rewir ...

is currently still being elucidated, but it has been proven to be active in regions of the

brain The brain is an organ (biology), organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. It consists of nervous tissue and is typically located in the head (cephalization), usually near organs for ...

closely linked to depression. It was found that leptin has

antidepressant Antidepressants are a class of medications used to treat major depressive disorder, anxiety disorders, chronic pain, and addiction. Common side effects of antidepressants include Xerostomia, dry mouth, weight gain, dizziness, headaches, akathi ...

-like effects similar to that of

selective serotonin reuptake inhibitors Selective serotonin reuptake inhibitors (SSRIs) are a class of drugs that are typically used as antidepressants in the treatment of major depressive disorder, anxiety disorders, and other psychological conditions. SSRIs primarily work by blo ...

(SSRIs). The discovery of leptin and its effects on appetite led to hopes of a treatment for obesity and type 2 diabetes, a major disease in the developed world. Unfortunately, clinical studies using leptin as a treatment for obesity in humans failed to show improvement, leading some scientists to conclude that the brain can become resistant to leptin, even at supra-physiological levels (the so-called "ceiling effect"), rendering treatment with leptin ineffective. However, although the notion of obesity as a state of 'leptin resistance' has become ingrained in the minds of many researchers, data does not directly support this contention. For example, the work of Rudolph Leibel at Columbia University shows that, in both obese and lean individuals, leptin injections do not reduce body mass. The finding that both lean and obese subjects have a similar lack of response underscores the notion that the brain is not designed to respond to increased leptin by decreasing food intake; rather, lack of leptin acts as a signal to increase food intake. Indeed, Leibel's work has shown that the decreases in serum leptin that occur post-weight-loss constitute a state of leptin deficiency, which drives increased appetite with weight loss. As such, leptin injections in weight-reduced patients can prevent increases in appetite and thereby allow patients to maintain weight loss. These studies, therefore, demonstrate that leptin treatment may be a useful strategy to treat obesity in humans, if not by driving weight loss directly then by allowing weight loss (as a result of diet and exercise) to be more readily maintained. Moreover, as geneticists learn more from the few cases of leptin gene mutations, the possibility remains that, although leptin was ineffective at treating obesity across the population, some individual obese patients might still benefit from its use as an anti-obesity medication. Research into the adipose-derived hormones adiponectin and resistin is ongoing. Like leptin, these hormones also affect energy balance and metabolism. Like leptin, observations in both humans and animal models have shown that adiponectin is relevant to insulin sensitivity and energy homeostasis. In contrast, the relationship between resistin and adiposity is not consistent between rodent models and human subjects (See Peter Arner, 2005: "Resistin: yet another adipokine tells us that men are not mice"); hence, the notion of resistin as a genuine adipose-derived hormone remains questionable.

References

{{reflist Peptide hormones Hormones of adipose tissue