GABAergic signaling by AgRP neurons prevents anorexia via a melanocortin-independent mechanism.
"AgRP neurons, also co-release neuropeptide Y (NPY) and γ-aminobutyric acid (GABA) to promote feeding and inhibit metabolism"
So the AgRP neurons also secret NPY and GABA, and this helps make you fat by suppressing the action of the POMC neurons, infact AgRP blocks the melanocortin 4 receptors, which is VERY bad news because blocking those receptors is a strong factor for bodyfat gain.
According to the abstract, removing the AgRP neurons essentially makes you stop eating and you die of starvation. So clearly the AgRP neurons are what makes you "hungry"
However, even if you delete the AgRP neurons, feeding behaviour can be restored by the administration of bretazenil, which is a GABA agonist. Interesting! So GABA receptor binding in the parabrachial nucleus plays a massive part in food intake.
Tuesday, 16 August 2011
Monday, 15 August 2011
Melanocortin 4 Receptor and Roux-en-Y Surgery
I rememberd reading on Stephen Guyenet's blog here about how weight loss surgery has no effect on those poor people with Melanocortin 4 receptor ( MC4R ) mutations, the link that Stephen gives in his blog is to a study that that looked at gastric banding surgery, which is actually significantly different from Roux-en-Y surgery.
In Roux-en-Y surgery, the ileum l-cell rich part of the intestine is moved right next to the entrance of the new stomach, but also, bile acids secreted from the gall bladder are given direct access to the rest of the ileum, which seems to cause hypersecretion of GLP-1 and results in intense stimulation of the POMC neurons.
I recently came across this study here that suggests that in actuality, even those people with MC4R receptor mutations may benefit from surgery aslong as it is Roux-en-Y.
I think this could be one of the strongest arguments yet for the power that incretins and bile acids play in bodyfat balance. Is it so powerful that it can even go someway as to help alleviate some the dreaded MC4R mutation effect of morbid obesity?
In Roux-en-Y surgery, the ileum l-cell rich part of the intestine is moved right next to the entrance of the new stomach, but also, bile acids secreted from the gall bladder are given direct access to the rest of the ileum, which seems to cause hypersecretion of GLP-1 and results in intense stimulation of the POMC neurons.
I recently came across this study here that suggests that in actuality, even those people with MC4R receptor mutations may benefit from surgery aslong as it is Roux-en-Y.
I think this could be one of the strongest arguments yet for the power that incretins and bile acids play in bodyfat balance. Is it so powerful that it can even go someway as to help alleviate some the dreaded MC4R mutation effect of morbid obesity?
Sunday, 14 August 2011
Neuropeptide Y - Insight into what it does
Moderate long-term modulation of neuropeptide y in hypothalamic arcuate nucleus induces energy balance alterations in adult rats.
Administration of leptin or insulin suppresses the expression of NPY (about 0.5 to 1.5-fold decrease of ARC NPY levels) and reduces food intake in lean rats and in rodent models with elevated NPY expression, such as ob/ob mice, fasted rats or diabetic rats.
NPY production is stimulated by negative energy conditions, such that food deprivation induces a potent up-regulation in the expression of NPY and AGRP (5–10 fold increase as compared to basal).
Furthermore, NPY levels return to initial values within 6 to 24 hours after re-feeding. (well that is good to know,)
In addition, some studies also report elevated levels of hypothalamic NPY (30%, in average) in diet-induced obese mice (DIO). However, other studies show a compensatory down-regulation of NPY expression in the ARC and immunoreactivity in the PVN in rats fed with high-fat diet for variable periods of time which was related to the inhibitor effect of elevated leptin concentrations.
Overall this study shows that a forced increase in basal NPY leads to extreme over-eating and extreme fat gain.
However
Reducing NPY strangely leads to normal feeding under basal circumstances, BUT, the mice did not increase thier food intake after a period of calorie restriction!
This suggests that the upregulation of NPY after calorie restriction is an essential survival mechanism. This is direct evidence that your body attempts to maintain a "bodyfat set-point", atleast with regards to under-feeding and forced adipose mass depletion.
Administration of leptin or insulin suppresses the expression of NPY (about 0.5 to 1.5-fold decrease of ARC NPY levels) and reduces food intake in lean rats and in rodent models with elevated NPY expression, such as ob/ob mice, fasted rats or diabetic rats.
NPY production is stimulated by negative energy conditions, such that food deprivation induces a potent up-regulation in the expression of NPY and AGRP (5–10 fold increase as compared to basal).
Furthermore, NPY levels return to initial values within 6 to 24 hours after re-feeding. (well that is good to know,)
In addition, some studies also report elevated levels of hypothalamic NPY (30%, in average) in diet-induced obese mice (DIO). However, other studies show a compensatory down-regulation of NPY expression in the ARC and immunoreactivity in the PVN in rats fed with high-fat diet for variable periods of time which was related to the inhibitor effect of elevated leptin concentrations.
Overall this study shows that a forced increase in basal NPY leads to extreme over-eating and extreme fat gain.
However
Reducing NPY strangely leads to normal feeding under basal circumstances, BUT, the mice did not increase thier food intake after a period of calorie restriction!
This suggests that the upregulation of NPY after calorie restriction is an essential survival mechanism. This is direct evidence that your body attempts to maintain a "bodyfat set-point", atleast with regards to under-feeding and forced adipose mass depletion.
Saturday, 13 August 2011
Leucine deprivation decreases fat cell volume
Unfortunately these studies did not show a reduction in fat cell number by apoptosis but they did show a marked reduction in fat cell volume, generally speaking it is fat cell number reductions that we want, but still these studies are interesting nonetheless.
Leucine deprivation decreases fat mass by stimulation of lipolysis in white adipose tissue and upregulation of uncoupling protein 1 (UCP1) in brown adipose tissue.
As we recently reported, mice maintained on a leucine-deficient diet for 7 days experienced a dramatic reduction in abdominal fat mass (9).
In our current study, we observed increases in lipolysis and expression of β-oxidation genes and decreases in expression of lipogenic genes and activity of fatty acid synthase (FAS) in WAT,
In addition, we observed for the first time that leucine deprivation increases expression of uncoupling protein (UCP)-1 in brown adipose tissue (BAT), suggesting increased thermogenesis.
The rapid fat loss induced by leucine deprivation suggested a possible increase in energy expenditure.
Serum free fatty acid (FFA) and glycerol levels were much lower in leucine-deprived mice than in pair-fed and control diet–fed groups
Consistent with these findings, no apoptosis was detected by Tdt-mediated dUTP nick end labeling (TUNEL) staining in mice maintained on a leucine-deficient diet
the results of the present study show that leucine deprivation significantly reduces body weight and abdominal adipose mass without affecting proportion of lean body mass
Mice maintained on a leucine-deficient diet, however, reduced their food intake by 15%. These results are consistent with previous studies showing that mice consume less food when provided with a diet deficient in essential amino acids
Fat mobilization in response to increased energy requirements is normally mediated via increased activities of the sympathetic nerve system
Leucine Deprivation Stimulates Fat Loss via Increasing CRH Expression in The Hypothalamus and Activating The Sympathetic Nervous System.
leucine deprivation stimulates fat loss by increasing expression of corticotrophin-releasing hormone in the hypothalamus
the effect of leucine deprivation on fat loss is mediated by activation of the sympathetic nervous system.
Leucine deprivation decreases fat mass by stimulation of lipolysis in white adipose tissue and upregulation of uncoupling protein 1 (UCP1) in brown adipose tissue.
As we recently reported, mice maintained on a leucine-deficient diet for 7 days experienced a dramatic reduction in abdominal fat mass (9).
In our current study, we observed increases in lipolysis and expression of β-oxidation genes and decreases in expression of lipogenic genes and activity of fatty acid synthase (FAS) in WAT,
In addition, we observed for the first time that leucine deprivation increases expression of uncoupling protein (UCP)-1 in brown adipose tissue (BAT), suggesting increased thermogenesis.
The rapid fat loss induced by leucine deprivation suggested a possible increase in energy expenditure.
Serum free fatty acid (FFA) and glycerol levels were much lower in leucine-deprived mice than in pair-fed and control diet–fed groups
Consistent with these findings, no apoptosis was detected by Tdt-mediated dUTP nick end labeling (TUNEL) staining in mice maintained on a leucine-deficient diet
the results of the present study show that leucine deprivation significantly reduces body weight and abdominal adipose mass without affecting proportion of lean body mass
Mice maintained on a leucine-deficient diet, however, reduced their food intake by 15%. These results are consistent with previous studies showing that mice consume less food when provided with a diet deficient in essential amino acids
Fat mobilization in response to increased energy requirements is normally mediated via increased activities of the sympathetic nerve system
Leucine Deprivation Stimulates Fat Loss via Increasing CRH Expression in The Hypothalamus and Activating The Sympathetic Nervous System.
leucine deprivation stimulates fat loss by increasing expression of corticotrophin-releasing hormone in the hypothalamus
the effect of leucine deprivation on fat loss is mediated by activation of the sympathetic nervous system.
Friday, 12 August 2011
Cutting calories to loose weight changes your brain
Obese reversal by a chronic energy restricted diet leaves an increased Arc NPY/AgRP, but no alteration in POMC/CART, mRNA expression in diet-induced obese mice.
"Arc neuropeptide Y (NPY) and agouti-related protein (AgRP) mRNA expression in DIO mice after obesity reversal were significantly higher than DIO mice without obesity reversal (17%, 47%, both p<0.05),"
This means that post obese mice will have lower energy expenditure, increased hunger, and an increased tendency to store fat mass.
"while the Arc pro-opiomelanocortin (POMC) and cocaine- and amphetamine-regulated transcript (CART) mRNA showed no difference."
" Both NPY and AgRP expression in DIO mice were negatively correlated with plasma leptin (R=-0.78, p<0.05; R=-0.72, p<0.05)."
" In conclusion, while chronic energy restriction will lead to weight loss, it can up-regulate hypothalamic orexigenic peptides, which may be an important contributing factor to weight regain after a weight loss program from an energy restricted diet."
"Arc neuropeptide Y (NPY) and agouti-related protein (AgRP) mRNA expression in DIO mice after obesity reversal were significantly higher than DIO mice without obesity reversal (17%, 47%, both p<0.05),"
This means that post obese mice will have lower energy expenditure, increased hunger, and an increased tendency to store fat mass.
"while the Arc pro-opiomelanocortin (POMC) and cocaine- and amphetamine-regulated transcript (CART) mRNA showed no difference."
" Both NPY and AgRP expression in DIO mice were negatively correlated with plasma leptin (R=-0.78, p<0.05; R=-0.72, p<0.05)."
" In conclusion, while chronic energy restriction will lead to weight loss, it can up-regulate hypothalamic orexigenic peptides, which may be an important contributing factor to weight regain after a weight loss program from an energy restricted diet."
Thursday, 11 August 2011
GLP-1 strikes again!
A novel human-based receptor antagonist of sustained action reveals body weight control by endogenous GLP-1.
"Daily administration of this antagonist by subcutaneous injection to diet-induced obese mice for 1 week caused a significant increase in food intake, body weight, and glucose intolerance, demonstrating endogenous GLP-1 as a relevant hormone in mammalian energy balance in the obese state."
"Daily administration of this antagonist by subcutaneous injection to diet-induced obese mice for 1 week caused a significant increase in food intake, body weight, and glucose intolerance, demonstrating endogenous GLP-1 as a relevant hormone in mammalian energy balance in the obese state."
Wednesday, 10 August 2011
Strength Training Research Summarised....
EVIDENCE-BASED RESISTANCE TRAINING RECOMMENDATIONS
Really good review of the clinical studies involving strength training, below the summary and recommendations from the article.....
*All credit goes to the authors of the above linked article ofcourse.
Intensity
Persons should train until momentary muscular failure to actively recruit all of the available motor units and muscle fibres, as opposed to a pre-determined number of repetitions.
Load and Repetition Range
Persons should self-select a weight >80% 1RM and perform repetitions to failure. Evidence suggests this is optimal for maximising strength and muscular endurance gains, whilst helping to improve bone mineral density.
Resistance Type
Persons should select resistance type based on personal choice, although evidence appears to suggest that resistance machines might have a lower risk of injury than free-weights.There appears to be no difference in strength gains between using free-weights, machines or other resistance types.Free weights and sport specific movements show no enhancement in sporting performance or force throughout that movement.
Repetition Duration
Persons should maintain steady force production throughout a range of motion, and reduce external forces such as momentum; movements should be of a pace that maintains muscular tension, not ballistic or explosive in nature.Faster movements cause greater peaks in both muscular and ground reaction forces which likely transfer through joints and connective tissue, potentially causing injury.
Volume of Exercise, Frequency and Periodization
Persons can obtain appreciably the same strength gains by performing only a single set of each exercise 1 x / 2 x week, compared to higher volume workouts.Persons should train when they feel physically and mentally ready to do so. Both physical and mental fatigue have the potential to negatively affect a workout and/or muscular growth and development.No specific periodized routine is unequivocally supported within the literature.
Genetics
Persons should consider their somatotype and that their genetics will dictate their muscular growth and development. Previous success with a routine is not evidence that it is optimal, genetic differences might dictate interpersonal differences in volume and frequency.
Really good review of the clinical studies involving strength training, below the summary and recommendations from the article.....
*All credit goes to the authors of the above linked article ofcourse.
Intensity
Persons should train until momentary muscular failure to actively recruit all of the available motor units and muscle fibres, as opposed to a pre-determined number of repetitions.
Load and Repetition Range
Persons should self-select a weight >80% 1RM and perform repetitions to failure. Evidence suggests this is optimal for maximising strength and muscular endurance gains, whilst helping to improve bone mineral density.
Resistance Type
Persons should select resistance type based on personal choice, although evidence appears to suggest that resistance machines might have a lower risk of injury than free-weights.There appears to be no difference in strength gains between using free-weights, machines or other resistance types.Free weights and sport specific movements show no enhancement in sporting performance or force throughout that movement.
Repetition Duration
Persons should maintain steady force production throughout a range of motion, and reduce external forces such as momentum; movements should be of a pace that maintains muscular tension, not ballistic or explosive in nature.Faster movements cause greater peaks in both muscular and ground reaction forces which likely transfer through joints and connective tissue, potentially causing injury.
Volume of Exercise, Frequency and Periodization
Persons can obtain appreciably the same strength gains by performing only a single set of each exercise 1 x / 2 x week, compared to higher volume workouts.Persons should train when they feel physically and mentally ready to do so. Both physical and mental fatigue have the potential to negatively affect a workout and/or muscular growth and development.No specific periodized routine is unequivocally supported within the literature.
Genetics
Persons should consider their somatotype and that their genetics will dictate their muscular growth and development. Previous success with a routine is not evidence that it is optimal, genetic differences might dictate interpersonal differences in volume and frequency.
Sunday, 7 August 2011
Brain control of fat metabolism
Brain insulin controls adipose tissue lipolysis and lipogenesis.
"Here, we show that insulin infused into the mediobasal hypothalamus (MBH) of Sprague-Dawley rats increases WAT lipogenic protein expression, inactivates hormone-sensitive lipase (Hsl), and suppresses lipolysis"
"Conversely, mice that lack the neuronal insulin receptor exhibit unrestrained lipolysis and decreased de novo lipogenesis in WAT. Thus, brain and, in particular, hypothalamic insulin action play a pivotal role in WAT functionality."
Hypothalamic control of lipid metabolism: focus on leptin, ghrelin and melanocortins.
"In mammals, neurons, particularly in the arcuate nucleus of the hypothalamus (ARC), are involved in the regulation of energy homeostasis. One regulatory pathway consists of neurons co-expressing neuropeptide Y (NPY) and agouti-related protein (AgRP), both potent stimulators of food intake, and an adjacent set of ARC neurons co-express proopiomelanocortin (POMC) and cocaine- and amphetamine-regulated transcript (CART), which suppress food intake."
"The anorectic effect of these drugs requires the accumulation of malonyl-CoA in the hypothalamus, which may be sensed as a signal of nutrient abundance by critical neurons regulating food intake (‘malonyl-CoA hypothesis’) and decreased expression of orexigenic (AgRP and NPY) and elevated expression of anorexigenic (CART, POMC) neuropeptides in the ARC"
"Leptin induces opposite effects on two ARC neuronal subpopulations: it directly inhibits the orexigenic NPY/AgRP-containing neurons and it stimulates the electrical activity of anorexigenic POMC neurons"
"One of the factors required by leptin to exert its anorectic effect is hypothalamic AMPK"
"suppression of AMPK activity in the medial hypothalamus is necessary for leptin’s anorexic and weight loss effects and that lack of suppression causes leptin resistance"
"The most relevant receptors in terms of energy balance regulation are MC3R and MC4R. Receptor agonist delivery into the hypothalamus reduces food intake, body weight and fat mass"
"Anatomical studies have demonstrated that central WAT sympathetic outflow neurons express MC4R"
" Central melanocortins modulate the norepinephrine turnover, which is the principal initiator of lipolysis in mammals. Norepinephrine is released from the sympathetic nerves innervating WAT, and the central injection of a MC3/4R agonist increased the norepinephrine turnover in specific fat depots"
Overall this is a very good study and needs to read in its entirety.
Hyperphagia and increased fat accumulation in two models of chronic CNS glucagon-like peptide-1 loss of function.
More evidence for the power of GLP-1 in obesity.
"Collectively, these data provide the strongest evidence to date that CNS GLP-1 plays a physiologic role in the long-term regulation of energy balance. Moreover, they suggest that this role is distinct from that of circulating GLP-1 as a short-term satiation signal."
"Here, we show that insulin infused into the mediobasal hypothalamus (MBH) of Sprague-Dawley rats increases WAT lipogenic protein expression, inactivates hormone-sensitive lipase (Hsl), and suppresses lipolysis"
"Conversely, mice that lack the neuronal insulin receptor exhibit unrestrained lipolysis and decreased de novo lipogenesis in WAT. Thus, brain and, in particular, hypothalamic insulin action play a pivotal role in WAT functionality."
Hypothalamic control of lipid metabolism: focus on leptin, ghrelin and melanocortins.
"In mammals, neurons, particularly in the arcuate nucleus of the hypothalamus (ARC), are involved in the regulation of energy homeostasis. One regulatory pathway consists of neurons co-expressing neuropeptide Y (NPY) and agouti-related protein (AgRP), both potent stimulators of food intake, and an adjacent set of ARC neurons co-express proopiomelanocortin (POMC) and cocaine- and amphetamine-regulated transcript (CART), which suppress food intake."
"The anorectic effect of these drugs requires the accumulation of malonyl-CoA in the hypothalamus, which may be sensed as a signal of nutrient abundance by critical neurons regulating food intake (‘malonyl-CoA hypothesis’) and decreased expression of orexigenic (AgRP and NPY) and elevated expression of anorexigenic (CART, POMC) neuropeptides in the ARC"
"Leptin induces opposite effects on two ARC neuronal subpopulations: it directly inhibits the orexigenic NPY/AgRP-containing neurons and it stimulates the electrical activity of anorexigenic POMC neurons"
"One of the factors required by leptin to exert its anorectic effect is hypothalamic AMPK"
"suppression of AMPK activity in the medial hypothalamus is necessary for leptin’s anorexic and weight loss effects and that lack of suppression causes leptin resistance"
"The most relevant receptors in terms of energy balance regulation are MC3R and MC4R. Receptor agonist delivery into the hypothalamus reduces food intake, body weight and fat mass"
"Anatomical studies have demonstrated that central WAT sympathetic outflow neurons express MC4R"
" Central melanocortins modulate the norepinephrine turnover, which is the principal initiator of lipolysis in mammals. Norepinephrine is released from the sympathetic nerves innervating WAT, and the central injection of a MC3/4R agonist increased the norepinephrine turnover in specific fat depots"
Overall this is a very good study and needs to read in its entirety.
Hyperphagia and increased fat accumulation in two models of chronic CNS glucagon-like peptide-1 loss of function.
More evidence for the power of GLP-1 in obesity.
"Collectively, these data provide the strongest evidence to date that CNS GLP-1 plays a physiologic role in the long-term regulation of energy balance. Moreover, they suggest that this role is distinct from that of circulating GLP-1 as a short-term satiation signal."
Saturday, 6 August 2011
Cross-talk between adipose and gastric leptins
Cross-talk between adipose and gastric leptins for the control of food intake and energy metabolism.
" In accordance with the lipostatic theory stated by Kennedy in 1953, leptin was originally discovered in white adipose tissue. Its expression by other tissues was later established."
"Among them, the gastric mucosa has been shown to secrete large amounts of leptin."
" However while adipose tissue secretes leptin in a slow constitutive endocrine way, the gastric mucosa releases leptin in a rapid regulated exocrine fashion into the gastric juice."
"Scrutiny into transport mechanisms revealed that a significant amount of the exocrine leptin crosses the intestinal wall by active transcytosis."
" Exocrine-secreted gastric leptin thus participates in a physiological axis independent in terms of time and regulation from that of adipose tissue to rapidly control food intake and nutrient absorption."
" In accordance with the lipostatic theory stated by Kennedy in 1953, leptin was originally discovered in white adipose tissue. Its expression by other tissues was later established."
"Among them, the gastric mucosa has been shown to secrete large amounts of leptin."
" However while adipose tissue secretes leptin in a slow constitutive endocrine way, the gastric mucosa releases leptin in a rapid regulated exocrine fashion into the gastric juice."
"Scrutiny into transport mechanisms revealed that a significant amount of the exocrine leptin crosses the intestinal wall by active transcytosis."
" Exocrine-secreted gastric leptin thus participates in a physiological axis independent in terms of time and regulation from that of adipose tissue to rapidly control food intake and nutrient absorption."
Insulin responsible for poor incretin response?
Insulin-dependent suppression of cholesterol 7α-hydroxlase is a possible link between glucose and cholesterol metabolisms.
cholesterol 7a-hydroxlase is the rate-limiting step for the synthesis of bile acids from cholesterol.
Is this why obese people have high cholesterol and poor postprandial bile acid/incretin responses?
Food for thought anyway.
cholesterol 7a-hydroxlase is the rate-limiting step for the synthesis of bile acids from cholesterol.
Is this why obese people have high cholesterol and poor postprandial bile acid/incretin responses?
Food for thought anyway.
Friday, 5 August 2011
Incretin's continued......
Role of incretins in the regulation of bone metabolism
"GIP has anabolic effects on bone mainly by stimulating osteoblastic bone formation through intermittent elevation of intracellular cAMP levels. On the other hand, GLP-1 is suggested to regulate bone resorption indirectly through the thyroid C cell."
Effects of GIP receptor antagonist for treatment of obesity
"GIP receptor antagonists possess favorable effects such as, decreased body adiposity or improvement of glucose intolerance through change of fat metabolism in high-fat diet induced or genetically induced obese experimental animals.
Loss of incretin effect is a specific, important, and early characteristic of type 2 diabetes.
Good review and free article.
Reversal of obesity and insulin resistance by a non-peptidic glucagon-like peptide-1 receptor agonist in diet-induced obese mice.
"Different from Boc5 treatment, caloric restriction did not affect adiposity significantly and circulating adipocytokines levels remained abnormal"
"These apparent differences imply that the regulatory role exerted by Boc5 (and hence, incretin mimetics in general) on lipid metabolism is independent of its inhibition on food intake."
Well well well, so much for the whole calorie restriction thing.
"Our results indicate that the basal glucose incorporation was significantly elevated in adipocytes isolated from obese mice while their response to insulin stimulation was severely impaired"
"the role of caloric restriction (pair-feeding) in modifying fat cell lipogenesis and lipolysis was minimal"
"GIP has anabolic effects on bone mainly by stimulating osteoblastic bone formation through intermittent elevation of intracellular cAMP levels. On the other hand, GLP-1 is suggested to regulate bone resorption indirectly through the thyroid C cell."
Effects of GIP receptor antagonist for treatment of obesity
"GIP receptor antagonists possess favorable effects such as, decreased body adiposity or improvement of glucose intolerance through change of fat metabolism in high-fat diet induced or genetically induced obese experimental animals.
Loss of incretin effect is a specific, important, and early characteristic of type 2 diabetes.
Good review and free article.
Reversal of obesity and insulin resistance by a non-peptidic glucagon-like peptide-1 receptor agonist in diet-induced obese mice.
"Different from Boc5 treatment, caloric restriction did not affect adiposity significantly and circulating adipocytokines levels remained abnormal"
"These apparent differences imply that the regulatory role exerted by Boc5 (and hence, incretin mimetics in general) on lipid metabolism is independent of its inhibition on food intake."
Well well well, so much for the whole calorie restriction thing.
"Our results indicate that the basal glucose incorporation was significantly elevated in adipocytes isolated from obese mice while their response to insulin stimulation was severely impaired"
"the role of caloric restriction (pair-feeding) in modifying fat cell lipogenesis and lipolysis was minimal"
Wednesday, 3 August 2011
Bile acid signalling, how important is it?
Bile-induced secretion of glucagon-like peptide-1: pathophysiological implications in type 2 diabetes?
"it has become clear that bile acids not only act as simple fat solubilizers, but additionally represent complex hormonal metabolic integrators."
"bile acids are ligands for the nuclear receptor FXR controlling transcription of genes involved in, for example, bile acid, cholesterol, and glucose metabolism"
"Bile acid activation of TGR5 results in increased intracellular cAMP levels, which in brown adipose tissue and muscle cells modulates energy expenditure by activating type 2 iodothyronine deiodinase, which in turn deiodinates thyroxine to the active thyroid hormone triiodothyronine"
"The reason for these limitations may be due to the fact that current GLP-1-based drugs exert their effects via elevated plasma levels of “GLP-1 receptor agonists”, and therefore, allegedly, may not elicit the local effects that endogenous secreted GLP-1 might have."
"Roux-en-Y gastric bypass (RYGB) surgery incurs remission of type 2 diabetes in the majority of patients (4), a “cure” of type 2 diabetes that has been linked to increased endogenous GLP-1 secretion"
"recent studies provide evidence for L cell expression of several G protein-coupled receptors (for example GPR120), which can be activated by long-chain fatty acids and, hence, result in GLP-1 secretion"
"Recently, the G protein-coupled receptor TGR5 was found in the enteroendocrine GLP-1-secreting cell line STC-1 (17) and in primary L cells from mice"
"These findings suggest that postprandial gall bladder contraction and increased flow of bile acids to the intestine potentiate nutrient-induced GLP-1 secretion from the L cells via TGR5 activation. "
"The newly described role of bile-induced TGR5 activation in L cell secretion combined with findings of reduced postprandial gall bladder emptying in type 2 diabetes (38, 39) [worsened by diabetic neuropathy typical for patients with long-standing disease (39)] suggests that reduced postprandial GLP-1 responses in patients with type 2 diabetes may, hypothetically, arise as a consequence of diabetic gall bladder dysmotility, which in turn might reduce postprandial bile flow to the intestine and, thereby, TGR5 activation in the L cells."
"Last, serum bile acids have been found to increase following RYGB (positively correlated with GLP-1 and negatively correlated with thyrotropic hormone) (33). As direct access of bile acids to L cell-rich parts of the small intestine is established following RYGB"
The Changes of Pro-opiomelanocortin Neurons in Type 2 Diabetes Mellitus Rats After Ileal Transposition: The Role of POMC Neurons.
"The Ileal transposition group demonstrated significantly improved plasma glucose homeostasis with increased glucagon-like peptide 1 secretion.
"associated with increased central neuronal activity with increased pro-opiomelanocortin and derivative gene expression in the hypothalamus and increased protein expression in the pituitary gland."
"More pro-opiomelanocortin neurons in the hypothalamus of diabetes rats were activated after ileal transposition. "
"it has become clear that bile acids not only act as simple fat solubilizers, but additionally represent complex hormonal metabolic integrators."
"bile acids are ligands for the nuclear receptor FXR controlling transcription of genes involved in, for example, bile acid, cholesterol, and glucose metabolism"
"Bile acid activation of TGR5 results in increased intracellular cAMP levels, which in brown adipose tissue and muscle cells modulates energy expenditure by activating type 2 iodothyronine deiodinase, which in turn deiodinates thyroxine to the active thyroid hormone triiodothyronine"
"The reason for these limitations may be due to the fact that current GLP-1-based drugs exert their effects via elevated plasma levels of “GLP-1 receptor agonists”, and therefore, allegedly, may not elicit the local effects that endogenous secreted GLP-1 might have."
"Roux-en-Y gastric bypass (RYGB) surgery incurs remission of type 2 diabetes in the majority of patients (4), a “cure” of type 2 diabetes that has been linked to increased endogenous GLP-1 secretion"
"recent studies provide evidence for L cell expression of several G protein-coupled receptors (for example GPR120), which can be activated by long-chain fatty acids and, hence, result in GLP-1 secretion"
"Recently, the G protein-coupled receptor TGR5 was found in the enteroendocrine GLP-1-secreting cell line STC-1 (17) and in primary L cells from mice"
"These findings suggest that postprandial gall bladder contraction and increased flow of bile acids to the intestine potentiate nutrient-induced GLP-1 secretion from the L cells via TGR5 activation. "
"The newly described role of bile-induced TGR5 activation in L cell secretion combined with findings of reduced postprandial gall bladder emptying in type 2 diabetes (38, 39) [worsened by diabetic neuropathy typical for patients with long-standing disease (39)] suggests that reduced postprandial GLP-1 responses in patients with type 2 diabetes may, hypothetically, arise as a consequence of diabetic gall bladder dysmotility, which in turn might reduce postprandial bile flow to the intestine and, thereby, TGR5 activation in the L cells."
"Last, serum bile acids have been found to increase following RYGB (positively correlated with GLP-1 and negatively correlated with thyrotropic hormone) (33). As direct access of bile acids to L cell-rich parts of the small intestine is established following RYGB"
The Changes of Pro-opiomelanocortin Neurons in Type 2 Diabetes Mellitus Rats After Ileal Transposition: The Role of POMC Neurons.
"The Ileal transposition group demonstrated significantly improved plasma glucose homeostasis with increased glucagon-like peptide 1 secretion.
"associated with increased central neuronal activity with increased pro-opiomelanocortin and derivative gene expression in the hypothalamus and increased protein expression in the pituitary gland."
"More pro-opiomelanocortin neurons in the hypothalamus of diabetes rats were activated after ileal transposition. "
Dairy pwns
Dairy attentuates oxidative and inflammatory stress in metabolic syndrome.
adequate-dairy decreased malondialdehyde and oxidized LDL at 7 d (35% and 11%, respectively; P < 0.01), with further decreases by 12 wk. Inflammatory markers were suppressed with intake of adequate-dairy, with decreases in tumor necrosis factor-α at 7 d and further reductions through 12 wk (35%; P < 0.05);
and a corresponding 55% increase in adiponectin at 12 wk (P < 0.01).
adequate-dairy significantly reduced waist circumference and trunk fat (P < 0.01 for both)
adequate-dairy decreased malondialdehyde and oxidized LDL at 7 d (35% and 11%, respectively; P < 0.01), with further decreases by 12 wk. Inflammatory markers were suppressed with intake of adequate-dairy, with decreases in tumor necrosis factor-α at 7 d and further reductions through 12 wk (35%; P < 0.05);
and a corresponding 55% increase in adiponectin at 12 wk (P < 0.01).
adequate-dairy significantly reduced waist circumference and trunk fat (P < 0.01 for both)
Subscribe to:
Posts (Atom)