Effects of BMP8B on AMPK Activation

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Questions and Answers

What was the observed increase in muscle mass when all three growth factors were inhibited?

75%

150% (correct)

45%

20%

What is the primary negative regulator of muscle mass that is highly expressed in skeletal muscle?

Activin B

BMP8B

Myostatin (correct)

Activin A

Which of the following areas is associated with the presence of brown adipose tissue (BAT) in adults?

Back of the neck (correct)

Palmar region

Plantars of the feet

Abdominal region

What process allows free fatty acids to produce heat within brown adipocytes?

Uncoupling process within mitochondria Signup and view all the answers

What was the main effect of centrally delivered BMP8B in the study?

Increased thermogenesis and decreased body weight Signup and view all the answers

What percentage increase in muscle mass results from inhibiting Myostatin?

45% Signup and view all the answers

Which area showed increased signaling due to reduced AMPK activation?

Lateral hypothalamic area (LHA) Signup and view all the answers

What metabolic change is observed in mice overexpressing FGF21?

Reduction in fat depot size Signup and view all the answers

What signaling pathway is activated in brown adipose tissue leading to thermogenesis?

PKA signaling pathway Signup and view all the answers

What is the role of FGF21 during prolonged fasting?

It activates fatty acid oxidation and ketone production. Signup and view all the answers

Which of the following statements about BMP8B is true?

It increases sympathetic activation of BAT. Signup and view all the answers

How does FGF21 affect body size in mice?

It causes a smaller body size due to growth hormone resistance. Signup and view all the answers

What physiological mechanism is triggered by higher doses of BMP8B?

Reduction of AMPK activation Signup and view all the answers

In which part of the body is FGF21 primarily produced?

Liver Signup and view all the answers

Which outcome is NOT associated with the effects of BMP8B?

Increased fat storage Signup and view all the answers

What is the primary role of myostatin in muscle development?

To regulate muscle mass negatively Signup and view all the answers

What happens to myostatin levels during exercise?

They decrease Signup and view all the answers

How does myostatin affect the phosphorylation of AKT protein kinase?

By reducing its phosphorylation Signup and view all the answers

Which proteins are induced as a result of SMAD activation caused by myostatin?

MERF1 and ATRG1 Signup and view all the answers

In the context of muscle mass, what is the net effect of myostatin activity?

Decreased protein synthesis and increased protein degradation Signup and view all the answers

What consequence does inactivity have on myostatin levels and muscle mass?

Increased myostatin levels and decreased muscle mass Signup and view all the answers

Which transcriptional pathway is activated by myostatin binding?

SMAD transcriptional pathway Signup and view all the answers

What do MERF1 and ATRG1 promote in muscle cells?

Protein breakdown Signup and view all the answers

Which of the following statements correctly describes myostatin's effects during muscle recovery?

It inhibits muscle regeneration through increased degradation Signup and view all the answers

What is the role of SMAD transcription factors in TGF-beta signaling?

They mediate the cellular effects of TGF-beta. Signup and view all the answers

Which growth factor is primarily responsible for allowing brown pre-adipocyte differentiation into brown adipocytes?

BMP7 Signup and view all the answers

What is the effect of deleting myostatin in mice?

Increased muscle mass. Signup and view all the answers

What happens to brown adipose tissue in BMP7 knockout (KO) mice?

It is significantly reduced in quantity. Signup and view all the answers

What percentage increase in muscle mass is observed when myostatin signaling is specifically blocked in adult mice?

30% Signup and view all the answers

Which pathway is primarily activated when TGF-beta proteins bind to their receptors?

SMAD signaling pathway. Signup and view all the answers

What additional factors must be blocked alongside myostatin to achieve significant weight loss?

All TGF-beta proteins Signup and view all the answers

How do TGF-beta proteins interact with cells?

By creating a ligand-receptor complex. Signup and view all the answers

Which of the following describes myostatin's role in skeletal muscle development?

Inhibits the differentiation of myoblasts. Signup and view all the answers

What effect did the delivery of follistatin have on muscle mass in the treated muscle compared to the control muscle?

Increase by 100% Signup and view all the answers

How does follistatin affect the interaction of myostatin with its receptors?

Prevents interaction Signup and view all the answers

What is the impact of BMP7 deficiency on UCP1 expression?

UCP1 expression is absent or very low. Signup and view all the answers

What does the term 'double muscle' phenotype refer to?

Increased muscle fibers and mass. Signup and view all the answers

What is indicated about the blocking of multiple TGF-beta proteins according to the experiment findings?

It is necessary for a significant increase in muscle mass Signup and view all the answers

Which growth factors are pivotal in the processes of adipogenesis and myogenesis?

Activin A and BMP7 Signup and view all the answers

What was the observed effect on muscle architecture after follistatin delivery?

No obvious detrimental effects observed Signup and view all the answers

Which ligands are most likely involved in the negative regulation of muscle mass along with myostatin?

Activin A and activin B Signup and view all the answers

What is the primary mechanism by which follistatin increases muscle mass in mice?

By promoting muscle fiber growth (hypertrophy) Signup and view all the answers

What was the time frame observed for the doubling of muscle mass in follistatin-treated muscles?

Four weeks Signup and view all the answers

Which of the following statements best describes the relationship between follistatin and myostatin?

Follistatin inhibits the inhibitory effects of myostatin Signup and view all the answers

Study Notes

BMP8B and AMPK Activation

Delivery of higher BMP8B doses centrally reduces AMPK activation in the ventromedial nucleus (VMN).
Decreased AMPK activation enhances signaling in the lateral hypothalamic area (LHA).
Resultant effects include increased sympathetic activation of brown adipose tissue (BAT), leading to heightened thermogenesis, elevated energy expenditure, and reduced body weight.
BMP8B also promotes increased browning of white adipose tissue (WAT).

FGF21 Overview

FGF21, primarily produced by the liver, plays a vital role in fuel utilization.
Overexpression in mice enhances fatty acid oxidation and ketogenesis during prolonged fasting.
This metabolic pathway helps supply fatty acids for ketogenesis when liver glucose production is inadequate.
Mice overexpressing FGF21 exhibit smaller body size mainly due to growth hormone resistance.

Growth Factors in Muscle and Fat Development

Specific growth factors influence the differentiation of mesenchymal stem cells into muscle, white, or brown adipose pathways, with BMP7 and myostatin as key examples.
BMP7 is essential for the differentiation of brown pre-adipocytes into functional brown adipocytes; its knockout results in decreased brown adipogenesis and little UCP1 expression.
Myostatin serves as a major negative regulator of muscle growth, inhibiting the differentiation of myoblasts.

Myostatin's Role in Muscle Mass Regulation

Myostatin impacts muscle mass by balancing protein synthesis and degradation.
Its signaling pathway involves SMAD transcription factors, reducing AKT phosphorylation and promoting muscle protein breakdown through FOXO3A nuclear translocation.
Increased myostatin levels during inactivity contribute to muscle mass loss, while exercise lowers its levels, facilitating muscle growth.

Follistatin and Muscle Mass Augmentation

Follistatin binds with high affinity to myostatin, preventing its action, and is shown to significantly enhance muscle mass in treated muscles.
Delivery of follistatin led to muscle mass doubling within four weeks, primarily through muscle fiber hypertrophy.
Targeting multiple TGF-beta proteins, including myostatin and activins, is crucial for substantial muscle mass increases.

Combined Inhibition of Growth Factors

Inhibition of Activin A and Activin B, along with myostatin, increases muscle mass significantly more than targeting myostatin alone.
Inhibition of all three growth factors resulted in a 150% increase in muscle mass, driving hypertrophy and functional improvements.

Brown Adipose Tissue (BAT) Management

Brown adipose tissue, found abundantly in rodents, persists in adults, particularly around the neck and upper body regions.
Sympathetic activation of BAT initiates PKA signaling, leading to the release of free fatty acids from lipid droplets.
UCP1 facilitates an uncoupling process in mitochondrial action during thermogenesis, essential for heat production, particularly in small mammals and infants.

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Description

This quiz explores the study on BMP8B and its impact on AMP kinase (AMPK) activation in the ventromedial nucleus. Key findings highlight the relationship between BMP8B administration and sympathetic activation in brown adipose tissue (BAT). Test your knowledge on this significant research topic.