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This thread is dedicated to the combination of most hormones that might have the most impact on fat loss and their interactions with each other and which should be kept high and which low. So here goes:
Insulin
By now we should know that insulin isn't the cause of fat gain. People might think it is because it increases lipogenesis, inhibits lipolysis and promotes fat storage. There is just one study I'd like to point out here.
In this study by Hall et al., they compared two groups: one reduced carbs and the other reduced fats, while keeping protein and calorie intake the same (1). The low carb group lost 53g/day of body fat, whereas the high carb diet lost 89g/day of body fat. At the end of the study, insulin decreased significantly in the low carb group and remained the same in the low-fat group. However, this did not prevent fat loss. Based on these findings, we can definitely reject the statement that carbohydrate restriction and insulin reduction is required for fat loss.
Plus, in a study by Hellerstein et al. they found that daily overfeeding with 150–200 g fat and 750–1000 g carbohydrates led to a de novo synthesis of 5 g fat per day, equivalent to < 3 % of the total fat consumed (2).
Carbohydrates are needed to support thyroid function, increase thyroid hormone conversion, keep glycogen stores full, stimulate glucose oxidation and speed up the metabolic rate, keep lipolysis under control, keep cortisol and adrenaline low, increase ATP and CO2 production, increase thermogenesis, glutathione synthesis, etc.
Leptin
Leptin, a hormone predominantly made by adipose cells, reduces hunger, stimulates energy expenditure (thermogenesis) via SNS, enhances the secretion of TRH, upregulating thyroid function, increases steroidogenesis, etc.
Although this might seem like a good hormone to keep high, thyroid hormones and leptin are inversely correlated and leptin and TSH are positively correlated. So actually, more leptin, higher TSH, more inflammation, etc. Obese people are also leptin resistant, hence hyperphagia.
Leptin inhibits hyperphagia by triggering the release of histamine in the hypothalamus, and histamine in turn prevents the downregulation of leptin receptors which mediates leptin resistance.
Histamine
People with high histamine, also known as histadelics, are generally slender and struggle to gain weight. Histamine increases lipolysis, leptin receptors and leptin sensitivity in the brain, reduces hunger, increases thermogenesis, etc. Histamine receptor H1 antagonism increases hunger and weight gain.
In a recent Chinese study, people received supplemental histidine (2 g, twice daily) or matching placebo, for 12 weeks. Insulin sensitivity improved significantly in the histidine-supplemented subjects, and this may have been partially attributable to loss of body fat. Body mass index (BMI), waist circumference and body fat declined in the histidine-supplemented group relative to the placebo group; the average fat loss in the histidine group was a robust 2.71 kg. Markers of systemic inflammation such as serum tumour necrosis factor-alpha (TNF-α) and interleukin (IL)-6, non-esterified fatty acids and oxidative stress also decreased in the histidine group (3). Food intake was slightly less on the histidine group, so it's not conclusive if the histidine increased energy expenditure and therefore fat loss or if the fat loss was a result of eating less calories.
Histidine competes with other neutral amino acids for transport into the brain, and BCAA levels are elevated in obesity, hence reduced histidine transport into the brain, resulting in fewer leptin receptors and low leptin sensitivity. Histidine supplementation might have restored leptin sensitivity and resulted in fat loss.
However, excess histamine increases serotonin synthesis, inhibits steroidogenesis (through H1, but actually promotes it through H2), promotes inflammation and is inversely correlated with thyroid hormones. Histamine reduces thyroid hormones, T4 and T3 (4) and thyroid administration reduce histamine levels (5). Anti-thyroid drugs alone decreases the sensitivity to histamine (6).
Cortisol is catabolic, reduces thyroid function, increases circulating BCAA, which might lead to low histamine levels in the brain and reduced metabolic rate.
Cortisol
Cortisol is a catabolic hormone, which inhibits steroidogenesis, increases the aromatase, inhibits thyroid hormone production (cortisol and TSH is correlated), conversion and function, slows the metabolic rate, inhibits thermogenesis, etc.
Adrenalectomy is associated with improvement of obesity and cold tolerance of models of genetic obesity lacking leptin or leptin signal. Evidence also suggests that glucocorticoids may inhibit the action of leptin. So cortisol lowers histamine in the brain and also promotes leptin resistance, slowing the metabolism.
Catecholamines (adrenaline & noradrenaline)
Catecholamines act on adrenoreceptors to exert its action. Alpha 2 adrenoceptor inhibits lipolysis, whereas the beta-adrenoceptors promotes lipolysis.
In a study by Hellstrom et al. they concluded that rapid weight losers were 10-fold more sensitive to the lipolytic effect of noradrenaline and 10-fold less sensitive to the antilipolytic effect induced by the alpha 2-adrenoceptor agonist clonidine than the slow weight losers (7).
"The rate of FFA and glycerol response to norepinephrine was increased twofold in the cells of obese subjects; no significant reutilization of FFA during catecholamine-induced lipolysis was observed in any of the groups (glycerol/FFA ratio near 1:3). There were no differences in the lipolytic sensitivity to beta 3- or beta 2-adrenoceptor specific agonists between the two groups. However, beta 3-adrenoceptor sensitivity was approximately 50 times enhanced (P = 0.0001), and the coupling efficiency of these receptors was increased from 37 to 56% (P = 0.01) in obesity. Furthermore, the obese subjects demonstrated a sixfold lower alpha 2-adrenoceptor sensitivity (P = 0.04). beta 3-Adrenoceptor sensitivity, but not alpha 2-, beta 1-, or beta 2-adrenoceptor sensitivity, correlated with norepinephrine-induced lipolysis (r = -0.67, P = 0.0001) and fat cell volume (r = -0.71, P = 0.0001). In conclusion, catecholamine-induced rate of FFA mobilization from omental fat cells is accelerated due to elevated rate of lipolysis in obesity, mainly because of an increased beta 3-adrenoceptor function, but partly also because of a decreased alpha 2-adrenoceptor function. This promotes an increased release of FFA to the portal system, which may contribute to the parallel metabolic disturbances observed in upper-body obesity." (8)
Obese individuals have elevated catecholamines, lipolysis and circulating free fatty acids, but no increase in the oxidation of the fats, hence metabolic syndrome. Boosting catecholamines and lipolysis even more would be really counterproductive, because the problem is elevated lipolysis. So fasting, intermittent fasting, low carb diets, etc, would make it worse by further promoting catecholamine and lipolysis.
Although alpha 2-adrenoceptors inhibit lipolysis, it also inhibits thyroid hormone secretion. In addition, TSH-induced thyroid hormone secretion is inhibited by alpha 1-adrenoceptor antagonism. So using alpha adrenoceptor agonists (catecholamines, clonidine) or antagonists (yohimbine), will just suppress thyroid function. Beta-adrenoceptors agonists (yohimbine, bitter orange extract, catecholamines, etc.) will also further promote lipolysis, suppress thyroid function and also glucose oxidation.
T3 reduces alpha-adrenoceptors, thus promoting normal lipolysis. The alpha 2-adrenergic response is completely inhibited in hypothyroid state, hence the out of control lipolysis (9).
Noradrenaline increases uncoupling, thyroid hormone conversion and significantly enhances lipolysis in the hyperthyroid state. Beta-adrenergic sensitivity and responsiveness are 10- and 2-fold increased, respectively, in hyperthyroid patients. In hypothyroid patients, beta-adrenoceptor responsiveness is reduced by 50%. The number of beta-adrenergic binding sites are doubled in hyperthyroid (10).
Noradrenaline actually inhibits lipolysis in the hypothyroid state, by binding mostly to alpha 2 adrenoceptors. So, even when trying to "tap" into the stress hormones for fat loss isn't going to do much when thyroid function is suboptimal.
Noradrenaline and thyroid hormones work in synergy, but are inversely correlated. High catecholamines mean low thyroid hormones, and vise versa.
Stimulation of UCP1 by norepinephrine alone, as judged by the denervation of brown adipose tissue (BAT) in hypothyroid rats, is quite modest, 2- to 3-fold, whereas the stimulation is 18- to 20-fold in the presence of thyroid hormones. Likewise, the stimulation of UCP1 by T3 on denervated BAT was also quite modest, barely significant. Both are needed for fat loss.
Endocannabinoids
Cannabinoid (CB) receptors and their putative ligands, arachidonylethanolamide (anand-amide) and 2-arachidonylglycerol (2-AG), activates the opioid receptor, that suppresses steroidogenesis, increases prolactin, promote lipolysis, etc. Blocking the CB1 receptor leads to fat loss.
Thyroid
TSH is elevated in obesity. Despite the higher plasma TSH levels, TSH receptors are less expressed on adipocytes of obese vs. lean individuals. This reduced TSH receptor expression might induce down-regulation of thyroid hormone receptors and thyroid hormone action, thereby further increasing plasma TSH and FT3 concentrations and constituting a condition of peripheral thyroid hormone resistance. So it might not help to supplement with thyroid, or this would increase thyroid requirements significantly, because of reduced thyroid receptors (11). Cortisol, leptin, histamine, estrogen, serotonin, endotoxins, PUFAs, oxidative damage, etc., all inhibit thyroid function and will result in a rise in the wrong hormones.
Both UCP1 expression and BAT temperature elevation in response to norepinephrine correlates nicely with TH receptor occupancy by T3 (12). Interestingly, transgenic mice with a disruption of the D2 gene (dio 2), were cold intolerance, in spite of normal plasma T3 concentration. DIO2 seem essential for uncoupling and thermogenesis and not necessarily total T3 levels.
Elevated T4 levels inhibit uncoupling, whereas T3 promotes it. Slow conversion of T4 to T3 will inhibit uncoupling. Cortisol, inflammation, sluggish liver function, fasting, etc., inhibits DIO2.
Serotonin (5-HT)
Inhibition of serotonin signaling or its synthesis in adipose tissue may be an effective treatment for obesity and its comorbidities (13).
5-HT inhibits thermogenesis through 5-HT3 in BAT and increased lipogenesis through 5-HT2a in WAT.
Ondansetron (a 5-HT3 antagonist) increased cyclic AMP production and phosphorylation of hormone-sensitive lipase (HSL) and protein kinase A substrate in the presence of the β3AR agonist.
5-HT1B inhibits dopamine is the frontal cortex, 5-HT2A increases prolactin and is significantly associated with obesity, 2-HT2C increases glucocorticoids, 5-HT4 are associated with estrogen receptors (14).
Reduced serotonin transporter (SERT) function is associated with obesity, insulin resistance (15). Sodium is a cofactor for SERT, and will directly aid in lowering serotonin.
Inhibition of 5-HT synthesis leads to inhibition of lipogenesis in epididymal white adipose tissue (WAT), induction of browning in inguinal WAT, activation of adaptive thermogenesis (UCP) in brown adipose tissue (BAT), DIO2, PGC-1a and increased mitochondrial number and size.
PUFAs (prostaglandins, leukotrienes), NO, cortisol, histamine, estrogen, increase TPH1, the enzyme that synthesizes serotonin.
Dopamine
Dopamine promotes energy expenditure and exploration. high dopamine makes you want to be active and use your senses. A common misconception of dopamine is that it's associated with addiction and obesity. However, increased dopamine does not promote the consumption of tasty food. The craving for tasty junk food is because of low dopamine, and the desire to increase it. When dopamine is high, there craving for sugar and other tasty foods fades away. High dopamine is essential for proper fat loss and the ability to stay on a healthy diet. Low dopamine promotes binge eating of easily obtainable, tasty, and most of the time, unhealthy foods.
Rats with elevated dopamine rats don’t go for easy food, but rather spend more time and energy to obtain more difficult to obtain food even when the reward is the same. A high carb diet promotes dopamine, whereas a low carb diet lowers dopamine.
Estrogen
The aromatase is elevated in obesity and hypothyroid and increased by inflammation, estrogen, serotonin, histamine, excess catecholamines, cortisol, etc.
Estrogen reduces insulin sensitivity, promotes inflammation and fat gain, inhibit thyroid hormone production, promotes lipolysis, inhibits uncoupling, etc.
Aromatase inhibitors most often promote fat loss and lean mass gains.
Testosterone and DHT
Testosterone increases the metabolic rate and lean mass retention and promotes the loss of bodyfat. Testosterone is converted the more potent androgen DHT, which cannot be aromatized. DHT reduced lipogenic enzymes and inhibited incorporation of fatty acid into triglyceride in adipocytes differentiated from preadipocytes from all fat depots. Supraphysiological doses of DHT does not significantly promote fat loss or lean mass gains.
It's been found that patients sufferings from muscle wasting because of AIDS, lose the most muscle when their DHT is low, even though their testosterone is normal. Patients with the most DHT, lost the least amount of lean mass (16). So DHT is high anti-catabolic and essential to keep high during fat loss.
Growth hormone
Growth hormone promotes lipolysis and is thought to aid in the retention of lean mass during fat loss. However, most studies only found a benefit to GH in GH deficient individuals. A GH deficiency seen obesity is a result of obesity and not a cause thereof, so trying to boost it is not the answer, and it might make the problem worse, by promoting lipolysis, insulin resistance and other side effects.
"Results: GH administered together with hypocaloric diets did not enhance fat loss or preserve lean tissue mass. No studies provided strong evidence for an independent beneficial effect of GH on visceral adiposity. In all but one study, glucose tolerance during GH treatment suffered relative to placebo.
Conclusion: The bulk of studies indicate little or no beneficial effects of GH treatment of obesity despite the low serum GH concentrations associated with obesity." (17) (this study is a highly recommended read on GH)
The "benefit" to GH is because of its conversion to IGF-1, yet the response to IGF-1 is blunted in obesity because of a reduction in IGF-1 binding proteins, leading to poor utilization.
Conclusion
It would be essential to keep cortisol, serotonin, growth hormone, estrogen as low as possible while optimizing thyroid hormone and androgen production as well as dopamine levels. Proper thyroid function will promote proper lipolysis and not pathological excessive lipolysis. Anything that will negatively affect thyroid function will result in a rise in the wrong hormones and negatively affect muscle retention and fat loss.
Things to avoid would be high tryptophan foods, PUFAs, endotoxins, nutrient deficiencies, low carb diet, etc.
Things to look into are excessive lipolysis inhibitors (niacinamide, aspirin), vitamin E, adrenaline antagonists (inosine, niacinamide), cortisol antagonists (glycine, magnesium, emodin, vitamin D, taurine, niacinamide, aspirin, etc), endotoxin antagonist (glycine, saturated fat, activated charcoal, cascara sagrada, etc.), optimize liver function, optimize digestion, DHT promotes (caffeine, glycine, niacinamide, androsterone, etc), etc.
That is all for now. If I missed anything, please add on if you wish. This thread is not to discuss which macros work best and if starches should be avoided or not, but mainly about which hormones are involved in fat loss.
Insulin
By now we should know that insulin isn't the cause of fat gain. People might think it is because it increases lipogenesis, inhibits lipolysis and promotes fat storage. There is just one study I'd like to point out here.
In this study by Hall et al., they compared two groups: one reduced carbs and the other reduced fats, while keeping protein and calorie intake the same (1). The low carb group lost 53g/day of body fat, whereas the high carb diet lost 89g/day of body fat. At the end of the study, insulin decreased significantly in the low carb group and remained the same in the low-fat group. However, this did not prevent fat loss. Based on these findings, we can definitely reject the statement that carbohydrate restriction and insulin reduction is required for fat loss.
Plus, in a study by Hellerstein et al. they found that daily overfeeding with 150–200 g fat and 750–1000 g carbohydrates led to a de novo synthesis of 5 g fat per day, equivalent to < 3 % of the total fat consumed (2).
Carbohydrates are needed to support thyroid function, increase thyroid hormone conversion, keep glycogen stores full, stimulate glucose oxidation and speed up the metabolic rate, keep lipolysis under control, keep cortisol and adrenaline low, increase ATP and CO2 production, increase thermogenesis, glutathione synthesis, etc.
Leptin
Leptin, a hormone predominantly made by adipose cells, reduces hunger, stimulates energy expenditure (thermogenesis) via SNS, enhances the secretion of TRH, upregulating thyroid function, increases steroidogenesis, etc.
Although this might seem like a good hormone to keep high, thyroid hormones and leptin are inversely correlated and leptin and TSH are positively correlated. So actually, more leptin, higher TSH, more inflammation, etc. Obese people are also leptin resistant, hence hyperphagia.
Leptin inhibits hyperphagia by triggering the release of histamine in the hypothalamus, and histamine in turn prevents the downregulation of leptin receptors which mediates leptin resistance.
Histamine
People with high histamine, also known as histadelics, are generally slender and struggle to gain weight. Histamine increases lipolysis, leptin receptors and leptin sensitivity in the brain, reduces hunger, increases thermogenesis, etc. Histamine receptor H1 antagonism increases hunger and weight gain.
In a recent Chinese study, people received supplemental histidine (2 g, twice daily) or matching placebo, for 12 weeks. Insulin sensitivity improved significantly in the histidine-supplemented subjects, and this may have been partially attributable to loss of body fat. Body mass index (BMI), waist circumference and body fat declined in the histidine-supplemented group relative to the placebo group; the average fat loss in the histidine group was a robust 2.71 kg. Markers of systemic inflammation such as serum tumour necrosis factor-alpha (TNF-α) and interleukin (IL)-6, non-esterified fatty acids and oxidative stress also decreased in the histidine group (3). Food intake was slightly less on the histidine group, so it's not conclusive if the histidine increased energy expenditure and therefore fat loss or if the fat loss was a result of eating less calories.
Histidine competes with other neutral amino acids for transport into the brain, and BCAA levels are elevated in obesity, hence reduced histidine transport into the brain, resulting in fewer leptin receptors and low leptin sensitivity. Histidine supplementation might have restored leptin sensitivity and resulted in fat loss.
However, excess histamine increases serotonin synthesis, inhibits steroidogenesis (through H1, but actually promotes it through H2), promotes inflammation and is inversely correlated with thyroid hormones. Histamine reduces thyroid hormones, T4 and T3 (4) and thyroid administration reduce histamine levels (5). Anti-thyroid drugs alone decreases the sensitivity to histamine (6).
Cortisol is catabolic, reduces thyroid function, increases circulating BCAA, which might lead to low histamine levels in the brain and reduced metabolic rate.
Cortisol
Cortisol is a catabolic hormone, which inhibits steroidogenesis, increases the aromatase, inhibits thyroid hormone production (cortisol and TSH is correlated), conversion and function, slows the metabolic rate, inhibits thermogenesis, etc.
Adrenalectomy is associated with improvement of obesity and cold tolerance of models of genetic obesity lacking leptin or leptin signal. Evidence also suggests that glucocorticoids may inhibit the action of leptin. So cortisol lowers histamine in the brain and also promotes leptin resistance, slowing the metabolism.
Catecholamines (adrenaline & noradrenaline)
Catecholamines act on adrenoreceptors to exert its action. Alpha 2 adrenoceptor inhibits lipolysis, whereas the beta-adrenoceptors promotes lipolysis.
In a study by Hellstrom et al. they concluded that rapid weight losers were 10-fold more sensitive to the lipolytic effect of noradrenaline and 10-fold less sensitive to the antilipolytic effect induced by the alpha 2-adrenoceptor agonist clonidine than the slow weight losers (7).
"The rate of FFA and glycerol response to norepinephrine was increased twofold in the cells of obese subjects; no significant reutilization of FFA during catecholamine-induced lipolysis was observed in any of the groups (glycerol/FFA ratio near 1:3). There were no differences in the lipolytic sensitivity to beta 3- or beta 2-adrenoceptor specific agonists between the two groups. However, beta 3-adrenoceptor sensitivity was approximately 50 times enhanced (P = 0.0001), and the coupling efficiency of these receptors was increased from 37 to 56% (P = 0.01) in obesity. Furthermore, the obese subjects demonstrated a sixfold lower alpha 2-adrenoceptor sensitivity (P = 0.04). beta 3-Adrenoceptor sensitivity, but not alpha 2-, beta 1-, or beta 2-adrenoceptor sensitivity, correlated with norepinephrine-induced lipolysis (r = -0.67, P = 0.0001) and fat cell volume (r = -0.71, P = 0.0001). In conclusion, catecholamine-induced rate of FFA mobilization from omental fat cells is accelerated due to elevated rate of lipolysis in obesity, mainly because of an increased beta 3-adrenoceptor function, but partly also because of a decreased alpha 2-adrenoceptor function. This promotes an increased release of FFA to the portal system, which may contribute to the parallel metabolic disturbances observed in upper-body obesity." (8)
Obese individuals have elevated catecholamines, lipolysis and circulating free fatty acids, but no increase in the oxidation of the fats, hence metabolic syndrome. Boosting catecholamines and lipolysis even more would be really counterproductive, because the problem is elevated lipolysis. So fasting, intermittent fasting, low carb diets, etc, would make it worse by further promoting catecholamine and lipolysis.
Although alpha 2-adrenoceptors inhibit lipolysis, it also inhibits thyroid hormone secretion. In addition, TSH-induced thyroid hormone secretion is inhibited by alpha 1-adrenoceptor antagonism. So using alpha adrenoceptor agonists (catecholamines, clonidine) or antagonists (yohimbine), will just suppress thyroid function. Beta-adrenoceptors agonists (yohimbine, bitter orange extract, catecholamines, etc.) will also further promote lipolysis, suppress thyroid function and also glucose oxidation.
T3 reduces alpha-adrenoceptors, thus promoting normal lipolysis. The alpha 2-adrenergic response is completely inhibited in hypothyroid state, hence the out of control lipolysis (9).
Noradrenaline increases uncoupling, thyroid hormone conversion and significantly enhances lipolysis in the hyperthyroid state. Beta-adrenergic sensitivity and responsiveness are 10- and 2-fold increased, respectively, in hyperthyroid patients. In hypothyroid patients, beta-adrenoceptor responsiveness is reduced by 50%. The number of beta-adrenergic binding sites are doubled in hyperthyroid (10).
Noradrenaline actually inhibits lipolysis in the hypothyroid state, by binding mostly to alpha 2 adrenoceptors. So, even when trying to "tap" into the stress hormones for fat loss isn't going to do much when thyroid function is suboptimal.
Noradrenaline and thyroid hormones work in synergy, but are inversely correlated. High catecholamines mean low thyroid hormones, and vise versa.
Stimulation of UCP1 by norepinephrine alone, as judged by the denervation of brown adipose tissue (BAT) in hypothyroid rats, is quite modest, 2- to 3-fold, whereas the stimulation is 18- to 20-fold in the presence of thyroid hormones. Likewise, the stimulation of UCP1 by T3 on denervated BAT was also quite modest, barely significant. Both are needed for fat loss.
Endocannabinoids
Cannabinoid (CB) receptors and their putative ligands, arachidonylethanolamide (anand-amide) and 2-arachidonylglycerol (2-AG), activates the opioid receptor, that suppresses steroidogenesis, increases prolactin, promote lipolysis, etc. Blocking the CB1 receptor leads to fat loss.
Thyroid
TSH is elevated in obesity. Despite the higher plasma TSH levels, TSH receptors are less expressed on adipocytes of obese vs. lean individuals. This reduced TSH receptor expression might induce down-regulation of thyroid hormone receptors and thyroid hormone action, thereby further increasing plasma TSH and FT3 concentrations and constituting a condition of peripheral thyroid hormone resistance. So it might not help to supplement with thyroid, or this would increase thyroid requirements significantly, because of reduced thyroid receptors (11). Cortisol, leptin, histamine, estrogen, serotonin, endotoxins, PUFAs, oxidative damage, etc., all inhibit thyroid function and will result in a rise in the wrong hormones.
Both UCP1 expression and BAT temperature elevation in response to norepinephrine correlates nicely with TH receptor occupancy by T3 (12). Interestingly, transgenic mice with a disruption of the D2 gene (dio 2), were cold intolerance, in spite of normal plasma T3 concentration. DIO2 seem essential for uncoupling and thermogenesis and not necessarily total T3 levels.
Elevated T4 levels inhibit uncoupling, whereas T3 promotes it. Slow conversion of T4 to T3 will inhibit uncoupling. Cortisol, inflammation, sluggish liver function, fasting, etc., inhibits DIO2.
Serotonin (5-HT)
Inhibition of serotonin signaling or its synthesis in adipose tissue may be an effective treatment for obesity and its comorbidities (13).
5-HT inhibits thermogenesis through 5-HT3 in BAT and increased lipogenesis through 5-HT2a in WAT.
Ondansetron (a 5-HT3 antagonist) increased cyclic AMP production and phosphorylation of hormone-sensitive lipase (HSL) and protein kinase A substrate in the presence of the β3AR agonist.
5-HT1B inhibits dopamine is the frontal cortex, 5-HT2A increases prolactin and is significantly associated with obesity, 2-HT2C increases glucocorticoids, 5-HT4 are associated with estrogen receptors (14).
Reduced serotonin transporter (SERT) function is associated with obesity, insulin resistance (15). Sodium is a cofactor for SERT, and will directly aid in lowering serotonin.
Inhibition of 5-HT synthesis leads to inhibition of lipogenesis in epididymal white adipose tissue (WAT), induction of browning in inguinal WAT, activation of adaptive thermogenesis (UCP) in brown adipose tissue (BAT), DIO2, PGC-1a and increased mitochondrial number and size.
PUFAs (prostaglandins, leukotrienes), NO, cortisol, histamine, estrogen, increase TPH1, the enzyme that synthesizes serotonin.
Dopamine
Dopamine promotes energy expenditure and exploration. high dopamine makes you want to be active and use your senses. A common misconception of dopamine is that it's associated with addiction and obesity. However, increased dopamine does not promote the consumption of tasty food. The craving for tasty junk food is because of low dopamine, and the desire to increase it. When dopamine is high, there craving for sugar and other tasty foods fades away. High dopamine is essential for proper fat loss and the ability to stay on a healthy diet. Low dopamine promotes binge eating of easily obtainable, tasty, and most of the time, unhealthy foods.
Rats with elevated dopamine rats don’t go for easy food, but rather spend more time and energy to obtain more difficult to obtain food even when the reward is the same. A high carb diet promotes dopamine, whereas a low carb diet lowers dopamine.
Estrogen
The aromatase is elevated in obesity and hypothyroid and increased by inflammation, estrogen, serotonin, histamine, excess catecholamines, cortisol, etc.
Estrogen reduces insulin sensitivity, promotes inflammation and fat gain, inhibit thyroid hormone production, promotes lipolysis, inhibits uncoupling, etc.
Aromatase inhibitors most often promote fat loss and lean mass gains.
Testosterone and DHT
Testosterone increases the metabolic rate and lean mass retention and promotes the loss of bodyfat. Testosterone is converted the more potent androgen DHT, which cannot be aromatized. DHT reduced lipogenic enzymes and inhibited incorporation of fatty acid into triglyceride in adipocytes differentiated from preadipocytes from all fat depots. Supraphysiological doses of DHT does not significantly promote fat loss or lean mass gains.
It's been found that patients sufferings from muscle wasting because of AIDS, lose the most muscle when their DHT is low, even though their testosterone is normal. Patients with the most DHT, lost the least amount of lean mass (16). So DHT is high anti-catabolic and essential to keep high during fat loss.
Growth hormone
Growth hormone promotes lipolysis and is thought to aid in the retention of lean mass during fat loss. However, most studies only found a benefit to GH in GH deficient individuals. A GH deficiency seen obesity is a result of obesity and not a cause thereof, so trying to boost it is not the answer, and it might make the problem worse, by promoting lipolysis, insulin resistance and other side effects.
"Results: GH administered together with hypocaloric diets did not enhance fat loss or preserve lean tissue mass. No studies provided strong evidence for an independent beneficial effect of GH on visceral adiposity. In all but one study, glucose tolerance during GH treatment suffered relative to placebo.
Conclusion: The bulk of studies indicate little or no beneficial effects of GH treatment of obesity despite the low serum GH concentrations associated with obesity." (17) (this study is a highly recommended read on GH)
The "benefit" to GH is because of its conversion to IGF-1, yet the response to IGF-1 is blunted in obesity because of a reduction in IGF-1 binding proteins, leading to poor utilization.
Conclusion
It would be essential to keep cortisol, serotonin, growth hormone, estrogen as low as possible while optimizing thyroid hormone and androgen production as well as dopamine levels. Proper thyroid function will promote proper lipolysis and not pathological excessive lipolysis. Anything that will negatively affect thyroid function will result in a rise in the wrong hormones and negatively affect muscle retention and fat loss.
Things to avoid would be high tryptophan foods, PUFAs, endotoxins, nutrient deficiencies, low carb diet, etc.
Things to look into are excessive lipolysis inhibitors (niacinamide, aspirin), vitamin E, adrenaline antagonists (inosine, niacinamide), cortisol antagonists (glycine, magnesium, emodin, vitamin D, taurine, niacinamide, aspirin, etc), endotoxin antagonist (glycine, saturated fat, activated charcoal, cascara sagrada, etc.), optimize liver function, optimize digestion, DHT promotes (caffeine, glycine, niacinamide, androsterone, etc), etc.
That is all for now. If I missed anything, please add on if you wish. This thread is not to discuss which macros work best and if starches should be avoided or not, but mainly about which hormones are involved in fat loss.
