Reviewer's report
Title:Infection with HIV and HCV enhances the release of Fatty Acid Synthase
into circulation: Evidence for a novel indicator of viral co-infection
Version: 1Date:1 February 2010
Reviewer: Munechika Enjoji
Reviewer's report:
This paper reports the findings that HIV-infected patients show significant
elevation of serum FASN levels compared with uninfected individuals and the
increase is greater in HCV co-infected patients. Authors are exploring the new
clinical possibility of measuring serum FASN concentrations in HIV-infected
patients, I think. However, in some points, I cannot understand authors’
explanation well.
Major comments
1. As is generally accepted, host lipid metabolism is frequently altered by antiviral
therapies. To get fundamental evidence, patients under antiviral treatments
should be excluded at first and authors should simply compare treatment-naïve
patients with control.
2. Circulating FASN may be from hepatocytes in HCV-infected patients. Where is
FASN mainly originated from, T cells, adipocytes, hepatocytes, muscle…? Is the
correlation between FASN and CD4 count meaning that T cells are the FASN
provider?
3. Authors think of estrogen as a stimulator of FASN expression. Why are FASN
levels in females (HIV+, HCV-) lower compared with males or control? Do you
mean that estrogen expression is suppressed by HIV infection? Fig 1B and C: in
female patients, HCV (infection to the liver) appears predominant effector for
FASN up-regulation.
4. Authors mentioned the association between the FASN levels and insulin
resistance many times. However, insulin resistance is not found in HOMA-IR in
patients (Table 2, 3). Please explain it.
5. “Hypercholesterolemia and low HDL-cholesterol levels were more prominent in
HCV co-infected patients and in those under PI treatment”, authors wrote. But no
evidences are found in the data (Table 2, 3).
6. Authors wrote, “FASN release is an active and controlled process through the
activation of AMPK” and “upon AMPK activation, the release of excess FASN
may provide a rapid mechanism to prevent further energy consumption”. In my
knowledge as a general notion, AMPK activation induces the suppression of
FASN and ACC which are enzymes for fatty acid synthesis. This appears
contrary to your explanation.
7. FASN and ALT levels show strong correlation and their concentration is much
higher in HCV+ patients (ALT levels are within the normal range in HCV-negative
patients). This means that their elevation results from cell death (mainly by liver
damage) and leakage?
8. As demonstrated in many studies, HCV infection directly induces FASN
expression in hepatocytes. Are there some similar pathways for FASN induction
in HIV-infected cells?
Minor comments
1. “Evidence for a novel indicator of viral co-infection” in the title means that
serum FASN concentration is clinically meaningful for HCV+HIV co-infection but
not for HIV infection?
Level of interest: An article of limited interest
Quality of written English: Needs some language corrections before being
published
Statistical review: No, the manuscript does not need to be seen by a
statistician.
Declaration of competing interests:
I declare that I have no competing interests
Reviewer's report
Title:Infection with HIV and HCV enhances the release of Fatty Acid Synthase
into circulation: Evidence for a novel indicator of viral co-infection
Version: 1Date:1 February 2010
Reviewer: Munechika Enjoji
Reviewer's report:
This paper reports the findings that HIV-infected patients show significant
elevation of serum FASN levels compared with uninfected individuals and the
increase is greater in HCV co-infected patients. Authors are exploring the new
clinical possibility of measuring serum FASN concentrations in HIV-infected
patients, I think. However, in some points, I cannot understand authors’
explanation well.
Major comments
1. As is generally accepted, host lipid metabolism is frequently altered by antiviral
therapies. To get fundamental evidence, patients under antiviral treatments
should be excluded at first and authors should simply compare treatment-naïve
patients with control.
2. Circulating FASN may be from hepatocytes in HCV-infected patients. Where is
FASN mainly originated from, T cells, adipocytes, hepatocytes, muscle…? Is the
correlation between FASN and CD4 count meaning that T cells are the FASN
provider?
3. Authors think of estrogen as a stimulator of FASN expression. Why are FASN
levels in females (HIV+, HCV-) lower compared with males or control? Do you
mean that estrogen expression is suppressed by HIV infection? Fig 1B and C: in
female patients, HCV (infection to the liver) appears predominant effector for
FASN up-regulation.
4. Authors mentioned the association between the FASN levels and insulin
resistance many times. However, insulin resistance is not found in HOMA-IR in
patients (Table 2, 3). Please explain it.
5. “Hypercholesterolemia and low HDL-cholesterol levels were more prominent in
HCV co-infected patients and in those under PI treatment”, authors wrote. But no
evidences are found in the data (Table 2, 3).
6. Authors wrote, “FASN release is an active and controlled process through the
activation of AMPK” and “upon AMPK activation, the release of excess FASN
may provide a rapid mechanism to prevent further energy consumption”. In my
knowledge as a general notion, AMPK activation induces the suppression of
FASN and ACC which are enzymes for fatty acid synthesis. This appears
contrary to your explanation.
7. FASN and ALT levels show strong correlation and their concentration is much
higher in HCV+ patients (ALT levels are within the normal range in HCV-negative
patients). This means that their elevation results from cell death (mainly by liver
damage) and leakage?
8. As demonstrated in many studies, HCV infection directly induces FASN
expression in hepatocytes. Are there some similar pathways for FASN induction
in HIV-infected cells?
Minor comments
1. “Evidence for a novel indicator of viral co-infection” in the title means that
serum FASN concentration is clinically meaningful for HCV+HIV co-infection but
not for HIV infection?
Level of interest: An article of limited interest
Quality of written English: Needs some language corrections before being
published
Statistical review: No, the manuscript does not need to be seen by a
statistician.
Declaration of competing interests:
I declare that I have no competing interests
Please review this paper.
user
Reviewer's report
Title:Infection with HIV and HCV enhances the release of Fatty Acid Synthase
into circulation: Evidence for a novel indicator of viral co-infection
Version: 1Date:1 February 2010
Reviewer: Munechika Enjoji
Reviewer's report:
This paper reports the findings that HIV-infected patients show significant
elevation of serum FASN levels compared with uninfected individuals and the
increase is greater in HCV co-infected patients. Authors are exploring the new
clinical possibility of measuring serum FASN concentrations in HIV-infected
patients, I think. However, in some points, I cannot understand authors’
explanation well.
Major comments
1. As is generally accepted, host lipid metabolism is frequently altered by antiviral
therapies. To get fundamental evidence, patients under antiviral treatments
should be excluded at first and authors should simply compare treatment-naïve
patients with control.
2. Circulating FASN may be from hepatocytes in HCV-infected patients. Where is
FASN mainly originated from, T cells, adipocytes, hepatocytes, muscle…? Is the
correlation between FASN and CD4 count meaning that T cells are the FASN
provider?
3. Authors think of estrogen as a stimulator of FASN expression. Why are FASN
levels in females (HIV+, HCV-) lower compared with males or control? Do you
mean that estrogen expression is suppressed by HIV infection? Fig 1B and C: in
female patients, HCV (infection to the liver) appears predominant effector for
FASN up-regulation.
4. Authors mentioned the association between the FASN levels and insulin
resistance many times. However, insulin resistance is not found in HOMA-IR in
patients (Table 2, 3). Please explain it.
5. “Hypercholesterolemia and low HDL-cholesterol levels were more prominent in
HCV co-infected patients and in those under PI treatment”, authors wrote. But no
evidences are found in the data (Table 2, 3).
6. Authors wrote, “FASN release is an active and controlled process through the
activation of AMPK” and “upon AMPK activation, the release of excess FASN
may provide a rapid mechanism to prevent further energy consumption”. In my
knowledge as a general notion, AMPK activation induces the suppression of
FASN and ACC which are enzymes for fatty acid synthesis. This appears
contrary to your explanation.
7. FASN and ALT levels show strong correlation and their concentration is much
higher in HCV+ patients (ALT levels are within the normal range in HCV-negative
patients). This means that their elevation results from cell death (mainly by liver
damage) and leakage?
8. As demonstrated in many studies, HCV infection directly induces FASN
expression in hepatocytes. Are there some similar pathways for FASN induction
in HIV-infected cells?
Minor comments
1. “Evidence for a novel indicator of viral co-infection” in the title means that
serum FASN concentration is clinically meaningful for HCV+HIV co-infection but
not for HIV infection?
Level of interest: An article of limited interest
Quality of written English: Needs some language corrections before being
published
Statistical review: No, the manuscript does not need to be seen by a
statistician.
Declaration of competing interests:
I declare that I have no competing interests
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