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Etymology:In Greek, leptos means thin
It is a protein hormone consisting of 167 amino acids.(Handbook of Biologically Active Peptides)
It circulates in the bloodstream and communicate between fat cells and the brain through the vagus nerve.
In simple words, Leptin means Satiety hormone.
Responds to both over and under-feeding.
Purpose:It helps to maintain fat store in time of starvation by playing the role of satiety hormone. Leptin works efficiently when the level of leptin in the blood and blood brain barrier is linear (Straight). When the level of blood leptin increases in case of obesity, the level of leptin transportation decreases in the Blood brain barrier. Leptin transportation in the blood brain barrier works efficiently under low leptin level blood condition.
This mechanism is biased because when you are in starvation mode, your blood leptin level drops and, in this case, blood brain barrier
leptin level increases to control your appetite, fat mass in short survival.
Leptin functions
Appetite
Thermo genesis
Neurogenesis, brain growth and memory
immune system.
All above benefits take place under low blood leptin level means low-fat percentage. Short-term fasting doesn’t change transport of leptin in the brain, but long-term starvation decreases or even stops transport of leptin in the brain.
Conclusion:This trigger your body is in starvation and this signal will change your metabolic rate like releasing rT3,decreasing GH.PMID: 16781741
The major protective role of leptin is to defend against reductions of body fat.
Our brain (Hypothalamus -arcuate nucleus) must receive the current status of stored body fat, nutrition status to regulate energy homeostasis and neuroendocrine system and this information is received by Leptin signal (afferent input) through vagus nerve PMID: 12525244.
Production:
Leptin is produced primarily in the adipocytes of white adipose tissue. It is also produced by brown adipose tissue, placenta, ovaries, skeletal muscle, stomach, mammary epithelial cells, bone marrow, gastric chief cells and P/D1 cells.
The amount of leptin released is directly related to the amount of body fat.
Subcutaneous fat appears to have a larger effect on absolute leptin concentrations.
Cortisol and Insulin stimulate Leptin secretion.
Why obese people have Leptin resistance or high blood Leptin level?
Ans: It is clear after adipose tissue is cultured in solution that Insulin and Cortisol stimulates Leptin. Short term Hyperinsulemia doesn’t impact on Leptin, but long term does (24 to 72hrs).PMID: 8826983
General Information:
1) At least 6 Leptin receptors Isomers have been identified until date.
Why obese people have huge hunger, appetite though they are carrying many body fat?
Ans:Long fasting raises blood triglycerides which gives rise to leptin resistance to increase feeding mode for survival along with decreasing calories’ expenditure, this signal of leptin is mistaken in obese body as a starvation PMID: 28990588.
In obese people (insulin resistance and T2D) there is a decrease in Leptin sensitivity, although they have high stored energy (fats) and high level of Leptin.
Leptin Resistance: “brain is starving, but your body is obese.”
Omega-6/3 ratio increases leptin resistance:Omega-6 causes an increase in endocannabinoid signaling which leads to leptin resistance because the endocannabinoid system is regulated by leptin, insulin, ghrelin, CCK PMID: 26950145.
Studies with respect to Omega-3 and Leptin are less clear. In a lean subject, leptin decreases and in an obese, leptin increases after leptin supplementation. Omega-3 reduces inflammatory cytokines, which helps to improve leptin sensitivity. Increase in leptin due to Omega-3 will prevent weight regain on calories restricted nutrition in obese PMID: 24129365
Why do you feel hungry at night on ketogenic nutrition? Why sleep disturbed on ketogenic nutrition? Why do you feel sleepy after eating a meal (high carbs)?
Ans: Melatonin increases Leptin in the presence of Insulin, decreases appetite while sleeping. PMID: 15572654
Without proper sleep, you can’t lose fat?
Ans:Sleep deprivation decreases Leptin level.PMID: 16459757
Why obese people have weak bone?
Ans:Leptin helps to regulate bone metabolism.PMID: 12419242
Why don’t we feel hungry in intermittent fasting?
Ans: Leptin plays a critical role in adaptation to starvation mode.PMID: 8717038 PMID: 19190071
Why intermittent fasting can’t be easy for prolong period of time?
Ans: Leptin level decreases after short-term fasting (24–72 hours) even though there is no fat loss.PMID: 12727933 PMID: 8866554 PMID: 8923877
Why appetite increase after chronic physical training?
Ans:
Why don’t You feel to have any food in emotional breakdown?
Ans:During emotional stress, Leptin increases.PMID: 17062814
Why do you feel hungry on low body fat percentage?
Ans:As you lose fat cells, circulating Leptin level gets drops which causes reversible decreases in thyroid activity, sympathetic tone, and
energy expenditure in skeletal muscle, and increases in muscle efficiency and parasympathetic tone.PMID: 18568083 PMID: 10882542
Somatotype and Leptin
ketogenic and leptin:Ketogenic nutrition increases serum leptin and decreases insulin. Several studies show ketogenic nutrition double the serum leptin
levels. Leptin reduces neuronal damage.PMID: 21856125
Leptin decreases even though BHB (Beta hydroxybutyrate) increases on calories’ deficit, and leptin increases after re-feeding with a decrease in BHB.
The more you do fasting, the more the body shifts from glucose to fat metabolism to generate glucose for the heart, brain and this happens. When leptin gets decreases because of which, it stimulates Hypothalamic pituitary axis, which leads to fat oxidation.PMID: 21856125
In RCT study (C-60,40,20 / F- 20,40,60 / Pro-20) found that there is an increase in energy expenditure for every 10% decrease in Carbohydrates also Leptin decreases while losing fat.
Leptin decreases insulin secretion from B-cells. Leptin helps prolong survival and protection of B-cells apoptosis. Increased fats storage of B-cells in type 1 and type 2 diabetes accelerates B-cell death. Endocrine glands highly express leptin and its receptor.
Leptin and thyroid hormone:Many studies have been conducted to known whether there is a relation between Leptin and Thyroid and many research fails and those researches were clinical based (Hyper or Hypo) taking into consideration many factors like bmi, autoimmune diseases, gender etc.
In one study, researchers found something related to Free Leptin, bound Leptin, Total Leptin in serum Leptin means free leptin is related to fat mass.PMID: 14514340
TSH Powerfully stimulates Leptin secretion. After incubation of Omental adipose tissue in TSH, there was clear stimulation of Leptin, this indicates a direct effect of TSH on Leptin but no direct effect of Prolactin, ACTH or FSH or LH. Though it’s a vitro study, it comes with advantages and disadvantages.
After Leptin Therapy In Congenital Leptin Deficiency patients, most of the weight loss was from fat mass. Leptin does not increase energy expenditure (metabolic rate) but prevent in reduction. Leptin therapy increases 24hr fats oxidation to a higher level than healthy people who are on a low calories diet from 9-20wk. Leptin therapy raises the basal level and stimulate LH and FSH. Leptin deficient people have irregular TSH pulsatile and circadian rhythms, leptin replacement does not increase free T3 or T4.18 months of Leptin therapy increases Grey matter in the brain.
TSH and Leptin have identical Circadian rhythm. Most children with leptin receptor mutation have hypothyroidism. Leptin stimulates thyroid functions by increasing thyrotropin-releasing hormone (TRH) secretion. Leptin can directly act on the thyroid gland because thyroid glands contain Leptin receptors . Prolonged fasting suppresses serum leptin, while suppressing thyroid stimulating hormone (TSH) secretion.PMID: 12727933 PMID: 10599995 PMID: 19889232
PMID: 9820621 PMID: 10749565
Leptin and Growth hormone (Fasting):Growth hormones gets secreted in one condition that is fasting.GH secretion is related with increase and decrease in adipose tissue i:eChanges in energy Homeostasis. Increase in free fatty acids (negative feedback loop) blocks secretion of GH and decrease in FFA
stimulates GH, and Leptin works as a messenger in this process.
GH works as a lipolysis and when FFA gets released it blocks GH but Leptin hormone, which also gets secreted while lipolysis stimulates GH
at the pituitary level through neuropeptide Y and blocking somatostatin in low glucose concentration. Leptin regulates some flow of GH.PMID: 10083898
Leptin and Catecholamines:Leptin stimulates the synthesis and secretion of catecholamines.
Leptin and Dopamine:Difference between Cheat meal and Refeed?
Ans: If a person is on calorie restriction for more than 3 months, also with Intermittent fasting and if the person hits a plateau level, then there are two options to break that plateau level without going too much into calorie deficit or increasing the fasting period the options are Cheat meal or Refeed, but the problem is what to choose? Let understand about cheat meal and Refeed. Cheat meal is also called a dirty meal because it is something is related to simple sugar, artificial flavors (Chinese food) or preservatives and other hand Refeed is related to increase in carbohydrates for 1 or 2 meal but Refeed meal is clean like increasing oats, brown rice, sweet potatoes etc. Both of these options have their benefits, Refeed purpose is to stimulate Leptin level and Cheat meal purpose is to stimulate dopamine level.(Central nervous system control of food intake and body weight) One can’t stimulate dopamine level just by Refeed meal. Dopamine:’Rewards’ stimulates the release of dopamine. Increases wanting of particular food or drug, wanting (hunger) and liking (craving) ordinarily occur.
How to break the plateau level?
Ans:Leptin signals the switch from fed to starved state. When Leptin concentration decreases in starvation, it decreases energy expenditure (fat lose) and it increases hunger.
Short-term carb overfeeding can bring leptin levels up (faster than fat is gained), this also increases Energy expenditure by 7% and the reason may be dietary thermogenesis, an increase in NEAT. The mechanism for these changes remains unknown. Leptin level can only increase with Carb intake and not by fat overfeed.PMID: 11126336
There is also one major reason behind carb overfeeding (cheat meal) is Leptin is not a marker of body composition. Leptin is a marker of fat mass, and Leptin is more accurate for males than for females.PMID: 10083898
Why don’t you hit plateau level in ketogenic nutrition more easily than carbohydrate Base nutrition? OR Why don’t you require cheat meal (Carbohydrates) in ketogenic nutrition to break plateau level?
Ans:As we know, one of the main fat burning hormones is GH and because of very fewer carbohydrates (ketogenic nutrition) which means low insulin level helps to regulate GH and on other hand, Leptin hormones help to maintain GH flow. As ketogenic nutrition is 70% to 80% fats which helps to maintain Leptin level and so helps to maintain GH secretion. So you don’t require cheat meal in ketogenic nutrition like in carbohydrate nutrition based to maintain Leptin level so to maintain GH and TSH for fat burning process which actually happens in Carbohydrates Base nutrition due to low leptin level on low body fat percentage. Losing 5% body fat at 20% and losing 5% fat at 10% creates total different response.
Leptin and Female
Women had 2±3 times higher leptin concentrations than men.PMID: 10792559
Leptin and sex hormones
Leptin and Training
PMID: 15293052
The effect of physical exercise on leptin concentrations is currently controversial. Some studies show an increase and some show a decrease in concentration. Lastly, it depends on duration and calories.PMID: 24259989
Conclusion:only prolonged endurance exercise (>60 min), >70% vo2max or Resistance training leads to a decrease in serum Leptin.
