Are you struggling to lose or gain weight?
People ask me all of the time why suddenly (or slowly) they lose or gain weight without changing their caloric intake or exercise levels.
The Selfhacked approach is to take a step back and think about the underlying physiology of weight regulation to see what’s going on. When you understand the biology of weight regulation, you can start trying to figure out what modifiable factors influence this biology.
I’ve found 32 hormones involved in weight regulation.
I’ve already discussed the big four hormones involved in obesity/anorexia – Insulin, Leptin, NPY, and Cortisol. So I won’t discuss these four here.
The following are other, relatively less important hormones that are involved in weight regulation.
Bottom Line: MSH causes weight loss.
MSH drastically reduces food intake .
Real world application: People with CIRS have lower MSH, and that’s why some of those people gain weight.
In healthy people, when fat stores are low, production of leptin from fat tissue is reduced and thus leptin falls. This leads to increased production of hunger-promoting factors such as NPY, Galanin, and AGRP and decreased levels satiety and energy expending factors such as a-MSH, CART and neurotensin .
α-MSH produced by neurons in the hypothalamus (arcuate nucleus) has important roles in the regulation of appetite and libido, while α-MSH secreted from the pituitary regulates the production of melanin.
Leptin increases a-MSH, which in turn decreases leptin, keeping the system balanced .
More about MSH:
MSH is also a broad spectrum anti-microbial hormone .
Low levels of MSH in part allows the immune system to go haywire in response to mold and also may lessen the clearance of the mold, since MSH is an anti-fungal hormone .
Low MSH is caused by a lack of sunlight, low cyclic AMP and leptin resistance (leptin helps create MSH).
Bottom Line: ACTH causes weight loss.
Real world application: People with CIRS have lower ACTH and that’s why some of these people gain weight. People with an overactive nervous system will have higher ACTH because it’s part of the stress response.
ACTH works on the melanocortin receptors, the same ones that a-MSH works on. So ACTH will cause weight loss in a similar manner to MSH.
ACTH enhances the release of fatty acids from fat tissue .
Bottom Line: Ghrelin causes weight gain.
Ghrelin is a fat increasing hormone that is secreted by an empty stomach and has been proposed to function as a meal initiator. It acts as an appetite stimulant in mice and humans  but also increases energy expenditure.
Ghrelin stimulates appetite in both lean and obese humans .
When given Ghrelin, normal rodent and humans ingest more food and become overweight .
When healthy volunteers were given ghrelin at a concentration similar to what you’d have after a 24 hour fast, food intake increased by ~30% (at a buffet-style meal) .
Interestingly in obese people, fasting ghrelin levels have been shown to be lower compared with normal weight controls and to rise following diet-induced weight loss. However, the typically expected post-meal fall in Ghrelin levels is also attenuated, or even absent in the obese .
Blocking Ghrelin (via ghrelin receptor antagonists and receptor knock-out animals) decreases food intake and body weight in rodents .
More about Ghrelin:
Ghrelin is somewhat of a cognitive enhancer. In the hippocampus, it promotes synapse formation in dendritic spines and LTP, which are paralleled by enhanced spatial learning and memory formation .
Bottom Line: Obestatin causes weight loss.
Obestatin is a hormone that is produced in the stomach and small intestine of several mammals including humans. Obestatin is a sister of ghrelin because they are produced from the same precursor – preproghrelin.
Obestatin was originally identified as a hormone that reduces food intake, but its effect on food intake remains controversial .
Ghrelin reversed the obestatin-induced inhibition of dopamine release, and obestatin was able to block ghrelin-induced inhibition of serotonin release .
5) Growth Hormone
Bottom Line: Growth hormone causes weight loss.
Growth hormone can induce fat busting (lipolysis). Impaired secretion of growth hormone in obesity results in the consequent loss of this fat-busting effect of growth hormone.
Growth hormone has a building (anabolic) effect by increasing insulin-like growth factor (IGF)-I.
Obese people treated with growth hormone over 12 weeks lost fat and gained muscle, in a randomized, double-blind and placebo-controlled trial.
Growth hormone treatment caused a 1.6-fold increase in the fraction of weight lost as fat and a greater loss of organ fat area than placebo treatment .
Bottom Line: CCK causes weight loss.
Real world application: People with high anxiety, a bloated gut, and reduced appetite will often have higher CCK, since this hormone causes all of these effects. Lectins stimulate CCK.
CCK, which is released mostly in response to fat, leads to suppression of appetite .
CCK injected into rodent brains reduces food intake .
CCK injected in the blood has been shown to reduce food intake in both rodents and humans, through a reduction in meal size and duration (CCKA=more important regulator of food intake) .
However, compensatory increases in meal frequency, the development of tolerance following infusion, and the short half-life of CCK undermines the therapeutic utility of giving it to people .
In rats bred without the CCKA receptor have increased meal sizes and this results in obesity, attributable to increased NPY .
A drug that binds to the CCKA receptor shows some properties of CCK, yet a 24-week double-blind randomized study in obese subjects showed no net reduction in body weight and no beneficial effects on waist circumference .
CCK as a stand-alone therapy, therefore, is not an effective anti-obesity tool , but perhaps in combination with other tools can be helpful.
Bottom Line: CRH causes weight loss.
Real world application: People with an overactive nervous system often have problems with gaining weight. This is in part because CRH, the stress hormone, causes weight loss.
CRH is an appetite suppressant .
Bottom Line: Testosterone causes weight loss.
Low baseline testosterone predicts obesity in men .
Long-term testosterone therapy in men with testosterone deficiency produces significant and sustained weight loss, a marked reduction in waist circumference and BMI, and improvement in body composition.
Testosterone therapy is associated with weight loss, and obesity is associated with reduced testosterone levels .
In animals, loss of the receptor for testosterone (AR) increases the number of fat cells and the accumulation of organ fat .
Normalization of testosterone levels reduces the activity of lipoprotein lipase and triglycerides .
Testosterone treatment results in increased muscle, less fat, improved insulin sensitivity, fat oxidation and reduction in fat mass – including organ fat .
Testosterone regulates carbohydrates, proteins and fat metabolism .
Testosterone deficiency contributes to fatigue via decreases mitochondrial function and therefore lower energy production and utilization .
Testosterone deficiency lowers energy production and utilization of food as energy, and this causes fat buildup .
Testosterone treatment in deficient men produced an increased quality of life with reduced fatigue, increased motivation, vigor, energy, libido, and erectile function and reduced waist circumference .
This results in more physical activity, thus resulting in increased energy utilization associated with increased muscle mass and improved mitochondrial function .
In contrast, testosterone/androgen deprivation therapy used in the management of hormone-dependent prostate cancer results in fatigue and reduces energy and motivation .
DHEA might have gender-specific effects.
In men given 100mg DHEA daily, fat body mass decreased 1.0 kg. In women, there was an increase in total body mass of 1.4 kg .
In women with anorexia, DHEA helped them gain weight 
Bottom Line: Estradiol causes weight loss.
Real world application: The clients I deal with are more likely to have higher estrogen, which may also suppress their weight.
11) Vitamin D
Vitamin D deficiency is highly prevalent in patients with obesity, and many studies have demonstrated the significant effect of vitamin D on fat cells.
In young adults, the dietary plus supplemental vitamin D intake was inversely related to the development of incident metabolic syndrome over 20 years of follow-up .
Vitamin D deficiency has been associated with obesity, organ fat, high triglycerides, and metabolic syndrome in Korean children .
In a 12-week double-blind, randomized clinical trial, vitamin D3 supplementation resulted in a statistically significant decrease in body fat mass in healthy and obese women compared with the placebo group .
The best form of vitamin D for use in the obese individuals is calcitriol because it is the active form of the vitamin D₃ metabolite, its receptors are present in fat cells, and it decreases inflammatory cytokines .
Bottom Line: Progesterone causes weight gain.
Progestin is a modified version of progesterone. Two studies that assessed body composition showed that progestin users had greater increases in body fat and decrease in muscle mass compared to users of non‐hormonal methods .
Pharmacological Progesterone treatment can reverse the hunger inhibitory effects of Estrogen in rats .
In humans, the frequency of binge eating varies with the menstrual cycle, with higher binge frequency occurring during the luteal phase when progesterone is higher .
Estrogen is associated with lower binge frequency, while Progesterone is associated with higher binge frequency in women with bulimia nervosa (BN) .
Also, in a community sample, higher emotional eating scores (consistent with binge eating) on an eating behavior questionnaire were obtained when Estrogen was low, and Progesterone was high .
Bottom Line: Melatonin causes weight loss.
Real world application: Circadian dysregulation is a common feature of people with fatigue and other health issues. Some people become obese and some people become thin for different reasons. But lower melatonin might play a role in the modern obesity epidemic.
Melatonin is involved in energy metabolism and body weight control in animals.
Many studies show that chronic melatonin supplementation in drinking water reduces body weight and abdominal fat in experimental animals, especially in the middle-aged rats and the weight loss effect did not require the animals to eat less and to be physically more active.
A potential mechanism is that melatonin promotes the recruitment of brown adipose tissue (BAT) as well as enhances its activity.
This effect would raise the basal metabolic rate by stimulating thermogenesis, heat generation through uncoupling oxidative phosphorylation in mitochondria .
14) Melanin-concentrating hormone (MCH)
Bottom Line: MCH causes weight gain.
Mice without MCH eat less and are lean. When it’s administered it increases food intake and weight gain. 
MCH 1 receptor-deficient mice are lean, hyperactive, gluttonous, and have an increased metabolism. The net effect is that they are thinner, even though they’re eating more. 
Bottom Line: Adiponectin causes weight loss.
Real world application: People with lectin sensitivity are more likely to have higher adiponectin, which causes weight loss.
Adiponectin is a hormone that is secreted by fat cells. It is different than most other hormones in that the production of the hormone falls as the number of fat cells increases. Levels of the hormone are inversely correlated with body fat percentage. So, the higher the adiponectin levels, the lower the body fat percentage.
Adiponectin increases insulin sensitivity by increasing tissue fat oxidation, resulting in reduced circulating fatty acid levels and reduced triglyceride contents in liver and muscle. This protein also suppresses cytokine production from macrophages .
16) Thyrotropin-Releasing Hormone (TRH)
Bottom Line: TRH causes weight loss.
Real world application: People with lectin sensitivity will be more likely to have higher TSH (and TRH probably as well), which contributes to weight loss.
TRH increases energy expenditure by increasing thyroid hormones. TRH also decreases appetite/food intake (contrary to T3), increases fat burning (thermogenesis), increases movement/energy expenditure and through its effects on the nervous system (in normal, fasting and stressed animals) .
TRH increases core body temperature, movement, and wakefulness, which increase energy expenditure .
TRH might suppress appetite through a leptin-mediated system . TRH neurons are connected to two types of leptin-responsive neurons in the arcuate nucleus a-MSH and CART, peptides that promote weight loss and increase energy expenditure .
NPY and AGRP are peptides that promote weight gain and reduce energy expenditure .
During fasting, MSH and CART decline (to stimulate eating), which causes TRH production to decline .
Simultaneously, an increase in NPY/AGRP reduces TRH (by increasing sensitivity to T3 inhibition) .
Bottom Line: TSH causes weight loss.
Real world application: People with lectin sensitivity will be more likely to have higher TSH, which contributes to weight loss.
TSH has been shown to reduce food intake when injected into the brains of rat .
TSH is involved with the seasonal alterations in food intake and body weight that occur in some species .
Check you TSH in this Thyroid Function Test.
18) Thyroid Hormones (T3)
Bottom Line: T3 causes weight loss.
Thyroid hormones quicken metabolism, but also increase appetite. And cause weight loss, generally, but other hormones are more important.
It is well established that the hypothalamic-pituitary-thyroid (HPT) axis regulates body weight.
Thyroid hormones are known to affect metabolic rate. Hypothyroidism classically causes reduced energy expenditure and weight gain .
Conversely, hyperthyroidism increases energy expenditure and reduces body weight .
T3 directly stimulates food intake at the level of the hypothalamus. In rodent models, T3 increases food intake .
T3 increases hypothalamic NPY and causes hunger (via Y1 receptor).
T3 also reduces hypothalamic POMC, which increases hunger (effect may be dose-dependent) .
However, the effects of thyroid hormones on food intake may not be mediated directly by the Arcuate nucleus (VMN) .
The VMN is likely to be the source of glutamatergic neurons that modulate ARC POMC neurons.
Hypothyroidism increases expression of the vesicular glutamate transporter vGLUT-2 in the anterior pituitary .
Activation of the Thyroid hormone (TRβ) receptor reduces body weight in obese rats .
Contrary to the actions of T3 to increase appetite, TRH has central effects to reduce food intake in normal, fasting and stressed animals .
T3 (or more specifically, thyroid hormones in general) are investigated for their interactions with fat mass since, in survey research, thyroid activity may be related to fat mass and BMI .
T3 supplementation is believed to have a muscle preserving effect, but not all studies agree .
However, at least one study has noted an increase in urinary nitrogen after four weeks of usage, in doses ranging from 0.36 – 1.01 mcg/kg bodyweight (R).
19) Glucagon-like peptide 1 (GLP-1)
Bottom Line: GLP-1 causes weight loss.
GLP-1 is a hormone that releases insulin and causes satiety.
In the gut, GLP-1 is in proportion to ingested calories .
In both lean and obese humans, GLP-1 lowers appetite, enhances satiety, reduces food intake, and causes weight loss. Some of these effects are from a reduction in gastric emptying and suppression of HCL secretion .
Obese individuals have been reported to have delays in the release of GLP-1 after meals and reduced GLP-1 .
GI surgery has been shown to increase GLP-1 levels .
Because of inactivation and clearance by the enzyme DPP-IV, the half-life of GLP-1 is an estimated 5 min, thus presenting a major hurdle down the path to its possible therapeutic utility. Currently investigated approaches against the short half-life of GLP-1 include DDP-IV inhibition and the development of more stable GLP-1 analogs .
GLP-1 reduces appetite by increasing serotonin release in the hypothalamus .
Infusion of GLP1 into the rat brain has been shown to improve associative and spatial memory in rats .
Bottom Line: Oxytocin causes weight loss.
Oxytocin injected into the brain of animals show decreased appetite, reduced food intake and shorter meal duration .
Also, oxytocin may also have a role in suppressing reward-related eating. Oxytocin can selectively suppress sugar intake, and it may have a role in limiting the intake of palatable food by inhibiting the reward pathway .
21) Peptide YY (PYY)
Bottom Line: PYY causes weight loss.
PYY is a gut hormone produced by intestinal cells co-secreted with GLP-1. Following food intake, PYY is released into the circulation .
PYY concentrations are proportional to meal energy content and peak levels appear 1 hour after a meal .
There are two forms: PYY (1 – 36) and PYY (3 – 36). The latter is produced by DPP-IV .
PYY (1 – 36) is an appetite stimulant, while PYY (3 – 36) is an appetite suppressant .
PYY (3 – 36) inhibits food intake for several hours in both rodents and people .
Animal studies have shown that the natural fermentation of dietary fiber by gut bacteria produces short-chain fatty acids such as propionate. These fatty acids stimulate the release of PYY (and GLP-1), which in turn suppress appetite. Propionate seems to be the most effective at stimulating PYY and GLP-1 release .
PYY3-36 levels are often lower in the obese state .
From a therapeutic utility standpoint, PYY3−36 has been shown to have hunger inhibiting effects in not only normal weight individuals but also in the obese .
In a trial consisting of both lean and obese humans, PYY (3 – 36) given intravenously led to a decrease in appetite and an almost 30% restriction in caloric intake in both groups .
Resistance is not thought to exist in the obese state to PYY (3-36) .
A PYY (3 – 36) nasal spray 3X/day resulted in modest weight reductions in humans. However, side effects including nausea and vomiting were encountered during clinical trials .
GI surgery has been shown to increase PYY levels .
It works by inhibition of NPY neurons and possible stimulation of the POMC neurons .
PYY (1 – 36) binds to and activates at least three Y receptor subtypes (Y1, Y2, and Y5), whereas PYY (3 – 36) is more selective for the Y2 receptor (Y2R) .
NPY neurons within the arcuate nucleus express the Y2R. In response to food ingestion PYY (3 – 36) rises within 15 min and plateau by approximately 90 min .
PYY (3 – 36) inhibited food intake in rodents and increased neuronal firing of the arcuate nucleus .
Mice missing Y2R are resistant to the hunger suppressing effects of PYY (3 – 36), suggesting that PYY (3 – 36) inhibits food intake through the Y2R (in the arcuate nucleus) .
In humans, infusion of PYY (3 – 36), at a dose which produced normal post-meal concentrations, significantly decreased appetite and reduced food intake by 33% over 24h .
Bottom Line: OXM causes weight loss.
Oxyntomodulin (OXM) shares the same precursor molecule as GLP-1 and is co-secreted with GLP-1 following a meal. Its release is proportional to meal calorie content .
In rodents, OXM reduces food intake and increases energy expenditure. OXM injections in rodents reduce body weight .
When given to humans, it increases satiation and reduces food intake, with repeated injections leading to decreases in body weight .
OXM also increases energy expenditure in humans .
The appetite reducing effects works on the same receptors as GLP-1 .
It is also possible that an unknown OXM receptor exists, yet it would almost certainly share similarities with the GLP-1 receptor .
Despite the probable involvement of the GLP-1 receptor in OXM signaling, the pathways are likely to separate .
Similar to GLP-1, the potential therapeutic utility of OXM may be hindered due to its inactivation by DPP-IV, although its effects on food intake in humans are more potent, and it is reported to cause less nausea than GLP-1 .
Bottom Line: VIP has mixed effects on weight.
Real world application: People with CIRS have lower VIP.
VIP is a very beneficial anti-inflammatory hormone/peptide in conditions of chronic inflammation.
VIP is interesting because it reduces appetite, but it may increase fat.
Injection of VIP inhibits appetite in mouse, chick, and goldfish .
In animal models, however, VIP may cause increased fat mass and less muscle (VIP receptor two deficient mice grow less, have increased metabolic rates and muscle, and decreased fat) .
VIP induces a significant decrease in physical activity, which in turn may result in increased fat mass .
VIP regulates circadian rhythms in clock neurons, which significantly influences weight. Loss of VIP abolished circadian firing rhythms in approximately half of all SCN neurons and disrupted synchrony between rhythmic neurons .
24) Insulin-Like Growth Factor-1 (IGF1)
Bottom Line: IGF-1 may cause weight gain.
Insulin increases IGF-1 and is similar to it, hence the name.
IGF-1 was shown to be an essential regulator of fat cell production .
Mice without working insulin and IGF-1 have markedly decreased white and brown fat mass and increased energy expenditure. However, they were unable to maintain body temperature when placed in cold because of less brown fat (which is burned to create heat) .
This could be part of the reason why people who are thin are also cold more – because they have less brown fat.
Bottom Line: Glucagon causes weight loss.
Glucagon is a hormone that breaks down stored glucose.
It also breaks down fat cells in humans under conditions of low insulin (such as Type 1 Diabetes) .
Bottom Line: Somatostatin causes weight loss.
In rats, food intake, body weight, and gut motility decrease after given Somatostatin .
In rats, food intake increased significantly during the night (in human equivalent), but decreased if it was given in the day .
The increase in food intake during the night may be explained by decreased Growth hormone. Growth hormone breaks down fat tissue and creates an energy pool in your blood to use, which decreases food intake .
Decreased gut flow also may explain the lower food intake and decreased body weight gain following Somatostatin treatment .
Bottom Line: Estrone causes weight loss.
In men, high estrone can cause anorexia, nausea, vomiting, edema, and feminization (including gynecomastia and erectile dysfunction) .
Bottom Line: Secretin causes weight loss.
When injected into mice, secretin reduces food intake. The mechanism works through the melanocortin system (which includes ACTH and MSH) .
The bottom lines in this article are often oversimplified and under-supported, but they are useful as a quick idea for people who don’t want to read further.
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