While it is well-established that leptin is involved in the regulation of the inflammatory response,    it has been further theorized that leptin's role as an inflammatory marker is to respond specifically to adipose-derived inflammatory cytokines.
In terms of both structure and function, leptin resembles IL-6 and is a member of the cytokine superfamily. Similar to what is observed in chronic inflammation, chronically elevated leptin levels are associated with obesity, overeating, and inflammation-related diseases, including hypertension , metabolic syndrome , and cardiovascular disease.
While leptin is associated with body fat mass, however, the size of individual fat cells, and the act of overeating, it is interesting that it is not affected by exercise for comparison, IL-6 is released in response to muscular contractions. Thus, it is speculated that leptin responds specifically to adipose-derived inflammation. Taken as such, increases in leptin levels in response to caloric intake function as an acute pro-inflammatory response mechanism to prevent excessive cellular stress induced by overeating.
When high caloric intake overtaxes the ability of fat cells to grow larger or increase in number in step with caloric intake, the ensuing stress response leads to inflammation at the cellular level and ectopic fat storage, i. The insulin increase in response to the caloric load provokes a dose-dependent rise in leptin, an effect potentiated by high cortisol levels.
This response may then protect against the harmful process of ectopic fat storage, which perhaps explains the connection between chronically elevated leptin levels and ectopic fat storage in obese individuals. Although leptin reduces appetite as a circulating signal, obese individuals generally exhibit a higher circulating concentration of leptin than normal weight individuals due to their higher percentage body fat.
A number of explanations have been proposed to explain this. An important contributor to leptin resistance is changes to leptin receptor signalling, particularly in the arcuate nucleus , however, deficiency of, or major changes to, the leptin receptor itself are not thought to be a major cause.
Other explanations suggested include changes to the way leptin crosses the blood brain barrier BBB or alterations occurring during development.
Studies on leptin cerebrospinal fluid CSF levels provide evidence for the reduction in leptin crossing the BBB and reaching obesity-relevant targets, such as the hypothalamus, in obese people. Since the amount and quality of leptin receptors in the hypothalamus appears to be normal in the majority of obese humans as judged from leptin-mRNA studies ,  it is likely that the leptin resistance in these individuals is due to a post leptin-receptor deficit, similar to the post-insulin receptor defect seen in type 2 diabetes.
When leptin binds with the leptin receptor, it activates a number of pathways. Mice with a mutation in the leptin receptor gene that prevents the activation of STAT3 are obese and exhibit hyperphagia. The PI3K pathway may also be involved in leptin resistance, as has been demonstrated in mice by artificial blocking of PI3K signalling. The PI3K pathway also is activated by the insulin receptor and is therefore an important area where leptin and insulin act together as part of energy homeostasis.
The consumption of a high fructose diet from birth has been associated with a reduction in leptin levels and reduced expression of leptin receptor mRNA in rats. Long-term consumption of fructose in rats has been shown to increase levels of triglycerides and trigger leptin and insulin resistance,   however, another study found that leptin resistance only developed in the presence of both high fructose and high fat levels in the diet.
A third study found that high fructose levels reversed leptin resistance in rats given a high fat diet. The contradictory results mean that it is uncertain whether leptin resistance is caused by high levels of carbohydrates or fats, or if an increase of both, is needed.
Leptin is known to interact with amylin , a hormone involved in gastric emptying and creating a feeling of fullness. When both leptin and amylin were given to obese, leptin-resistant rats, sustained weight loss was seen. Due to its apparent ability to reverse leptin resistance, amylin has been suggested as possible therapy for obesity. It has been suggested that the main role of leptin is to act as a starvation signal when levels are low, to help maintain fat stores for survival during times of starvation, rather than a satiety signal to prevent overeating.
Leptin levels signal when an animal has enough stored energy to spend it in pursuits besides acquiring food. Dieters who lose weight, particularly those with an overabundance of fat cells, experience a drop in levels of circulating leptin. This drop causes reversible decreases in thyroid activity, sympathetic tone, and energy expenditure in skeletal muscle, and increases in muscle efficiency and parasympathetic tone.
A decline in levels of circulating leptin also changes brain activity in areas involved in the regulatory, emotional, and cognitive control of appetite that are reversed by administration of leptin.
Osteoarthritis and obesity are closely linked. Obesity is one of the most important preventable factors for the development of osteoarthritis. Originally, the relationship between osteoarthritis and obesity was considered to be exclusively biomechanically based, according to which the excess weight caused the joint to become worn down more quickly.
However, today we recognise that there is also a metabolic component which explains why obesity is a risk factor for osteoarthritis, not only for weight-bearing joints for example, the knees , but also for joints that do not bear weight for example, the hands. Thus, the deregulated production of adipokines and inflammatory mediators, hyperlipidaemia, and the increase of systemic oxidative stress are conditions frequently associated with obesity which can favour joint degeneration.
Furthermore, many regulation factors have been implicated in the development, maintenance and function, both of adipose tissues, as well as of the cartilage and other joint tissues. Alterations in these factors can be the additional link between obesity and osteoarthritis. Adipocytes interact with other cells through producing and secreting a variety of signalling molecules, including the cell signalling proteins known as adipokines.
Certain adipokines can be considered as hormones, as they regulate the functions of organs at a distance, and several of them have been specifically involved in the physiopathology of joint diseases. In particular, there is one, leptin, which has been the focus of attention for research in recent years.
The circulating leptin levels are positively correlated with the Body Mass Index BMI , more specifically with fatty mass, and obese individuals have higher leptin levels in their blood circulation, compared with non-obese individuals. In addition to the function of regulating energy homeostasis, leptin carries out a role in other physiological functions such as neuroendocrine communication, reproduction, angiogenesis and bone formation. More recently, leptin has been recognised as a cytokine factor as well as with pleiotropic actions also in the immune response and inflammation.
Leptin has thus emerged as a candidate to link obesity and osteoarthritis and serves as an apparent objective as a nutritional treatment for osteoarthritis. As in the plasma, the leptin levels in the synovial fluid are positively correlated with BMI.
Leptin has been shown to be produced by chondrocytes, as well as by other tissues in the joints, including the synovial tissue, osteophytes, the meniscus and bone. The risk of suffering osteoarthritis can be decreased with weight loss. This reduction of risk is related in part with the decrease of the load on the joint, but also in the decrease of fatty mass, the central adipose tissue and the low-level inflammation associated with obesity and systemic factors.
This growing evidence points to leptin as a cartilage degradation factor in the pathogenesis of osteoarthritis, and as a potential biomarker in the progression of the disease, which suggests that leptin, as well as regulation and signalling mechanisms, can be a new and promising target in the treatment of osteoarthritis, especially in obese patients.
Obese individuals are predisposed to developing osteoarthritis, not only due to the excess mechanical load, but also due to the excess expression of soluble factors, that is, leptin and pro-inflammatory cytokines, which contribute to joint inflammation and cartilage destruction. As such, obese individuals are in an altered state, due to a metabolic insufficiency, which requires specific nutritional treatment capable of normalising the leptin production and reducing the systematic low-level inflammation, in order to reduce the harmful impact of these systematic mediators on the joint health.
There are nutritional supplements and pharmacological agents capable of directing these factors and improving both conditions. Leptin was approved in the United States in for use in congenital leptin deficiency and generalized lipodystrophy. An analog of human leptin metreleptin trade name Myalept was first approved in Japan in , and in the United States in February In the US it is indicated as a treatment for complications of leptin deficiency, and for the diabetes and hypertriglyceridemia associated with congenital or acquired generalized lipodystrophy.
From Wikipedia, the free encyclopedia. Not to be confused with Lectin or Lecithin. Structure of the obese protein leptin-E Leptin plays a critical role in the adaptive response to starvation. Leptin receptor and Energy expenditure. Bearing in mind that other hormones such as ghrelin operate in a faster-time scale, it would be misleading to define it as "the satiety hormone". Nat Clin Pract Endocrinol Metab.
World Rev Nutr Diet. Crit Rev Food Sci Nutr. Journal of Clinical Investigation. A complex hub among inflammation, metabolism, and immunity". The Inside Story of the Obesity Industry. RNA expression pattern and mapping on the physical, cytogenetic, and genetic maps of chromosome 7". Wei Sheng Yan Jiu in Chinese. Studies in lean and obese subjects and during short-term fasting". Int J Sports Med. Studies in vivo and in vitro". Journal of Cellular Biochemistry.
Lay summary — medicinenet. The Journal of Neuroscience. International journal of obesity Lond. Lay summary — WebMD. Arterioscler Thromb Vasc Biol. Current Opinion in Obstetrics and Gynecology. Cell and Tissue Research. Focus on "Fructose-induced leptin resistance exacerbates weight gain in response to subsequent high-fat feeding," by Shapiro et al". Annals of the Rheumatic Diseases.
Current Opinion in Rheumatology. Insights from mouse models of obesity". Clinical and Experimental Rheumatology. Journal of Orthopaedic Research: Official Publication of the Orthopaedic Research Society. Contribution of joint tissues to their articular production". Survey of the effects of W on inflammatory mediators produced by OA cartilage as detected by protein antibody array".
Retrieved 30 April Thyroid hormones T 3 T 4 Calcitonin Thyroid axis. Glucagon Insulin Amylin Somatostatin Pancreatic polypeptide. Eptinezumab Erenumab Fremanezumab Galcanezumab. Corticorelin Corticotropin releasing hormone Sauvagine Urocortin Antagonists: Galanin Galanin Galmic Galnon Antagonists: Dasiglucagon Glucagon Oxyntomodulin Antagonists: Melanin concentrating hormone Antagonists: Neurotensin Neuromedin N Antagonists: There are mobile device apps that you can use to track daily tasks.
You can make an Excel spreadsheet and keep it updated. Or you can use an "old school" technique like the water card. How to make a water card: Create a word processing document or Excel to make a 9X5 card with grids, include the days of the week and a block for each 8 ounce glass of water or equivalent. You are more likely to succeed if you turn the water habit into an easy process. Here are nine ways you can make water a convenient resource in your life:. I have a big sign on my refrigerator.
Every time I make lunch, breakfast or dinner, I see this reminder and remember to have a tall glass of water. Reminders in any shape and form can help you to get in your daily water. Put it on "to-do list. Set audible reminders on your PC, watch or mobile device. Do whatever it takes to remember this new routine. Or try Crystal Light which has a variety of different flavors.
But, I also have the habit of being a "two-fisted" drinker--one tea and a glass of water OR one beer and a glass water. This routine serves two purposes. Second, it helps me maintain my daily hydration. T his one is simple and easy to follow. I like a good jolt of caffeine in the morning, but I make myself drink three glasses of water before indulging in caffeine. Here are 3 of the best water filter pitchers you can use at home. Your body can be a bit sneaky. Sometimes when you need water it can feel like you are hungry.
Some people grab that Mars Bar and slam down unneeded calories. It's far better to drink a bit of water the next time you feel hungry. Then, if the hunger persists…eat and drink water while eating.
Convenience and tracking are great ways to get in your daily requirements of water, but you also want to make it more palatable. Do it this way and look forward to getting your daily fill of high quality H2O. You can add a variety of ingredients to make water taste better:. Personally, I can't stand the taste of "sugar free" drinks, but some people find that adding them to water makes it taste a whole lot better. Yes, crystal light does count as water intake, but sugar substitutes bring their own issues, so use sparingly.
You can try this: You can add flavor, or fruit if you want. Take them out in the morning and drink them throughout the day for ice cold water. Try to finish them all. Having everything prepared before hand is a simple way to track your water intake.
By pre-planning your water intake, all you'll have to remember is to create the water each night and drink every bottle you fill. Check out this article for great tips for getting your enough water daily. Another great option is to try carbonated water.
According to the Mayo Clinic, carbonated water is every bit as healthy as tap water, with no adverse effects on the body.
Sometimes that bubbly and effervescent water can hit the spot. Add this to the idea of flavoring your carbonated water and you could have a big hit that hill help keep you hydrated. Keep the flavoring non-sugar, non-aspartame and all natural, of course! There are lots of good options for these carbonation machines. The one pictured here is a very good one. It carbonates 1 liter at a time, using cannisters good for carbonating 60 liters of water.
There are fancier and bigger carbonators out there, but for the price this water carbonator is the best rated. In fact there are 60 different flavoring available for this home seltzer water maker.
There are all natural flavorings and non-asparatme and non-high fructose corn syrup options. Being an advocate of pure water I would highly recommend sticking to natural flavorings only, however.
In my opinion, increasing your water intake is one of the simplest, but most effective routines you can add to your life. Simply follow the strategies I've outline in this post and you'll form a habit that will make you healthier, happier and more likely to form other positive, life-changing habits.
Finally, when you've mastered this habit, I encourage you to try some simple workout routines or increasing your daily step count. Both are simple routines that can produce a dynamic change to your weight and overall fitness level. Like this post on daily water intake? Then share the below image on your favorite social media website like Pinterest!
And share the benefits of water with others. A Lesson From the Air Force Help Kidney Function According to this New York Times wellness article, a moderate increase in water consumption can clear sodium, urea and toxins from the body, decreasing the likelihood of kidney related problems and even kidney stones. Create a Youthful Appearance. Oxygenates the blood Removes toxins from the blood Increases Lymph production Cleans eyes Cleans mouth Helps digest food Helps fight insomnia Lubricates joints Increases Serotonin Production fights depression Track your water intake I am a firm believer in tracking.
Get your own pure and clean water from home. Make Water More Convenient. Here are nine ways you can make water a convenient resource in your life: Carry a water bottle everywhere. Make it taste good.