Clinical Applications of Biomarkers, Lipoprotein Testing
292
The Role of the Novel Lipokine Palmitoleic
Acid in Cardiovascular Health: from Bench to
Bedside*
Zhi-Hong Yang, PhD, Milton Pryor, BS,
Maureen Sampson, BS, Alexander Sorokin, MD, PhD,
Marcelo Amar, MD,
Alan Remaley, MD, PhD, (Bethesda, MD)
Lead Author’s Financial Disclosures: None.
Study Funding: None.
Background/Synopsis: Cardiovascular disease (CVD)
is a major healthcare problem worldwide and is known to
be greatly affected by diet. Consumption of monounsatu-
rated fatty acids (MUFA) has favorable effects on CVD
risk. Compared with oleic acid (C18:1 n-9) that is the most
common dietary MUFA, there is limited information on the
cardiovascular effects of other dietary MUFAs, such as
palmitoleic acid (PA; C16:1 n-7) that has been recently
identified as a novel lipokine coordinating homeostasis.
Objective/Purpose: The objective of our studies was
to investigate the physiologic effect, particularly cardio-
protective impact, of PA in animal models and human
subjects.
Methods: Three animal studies were performed to
investigate the effect of dietary PA on lipid/glucose
metabolism, atherosclerotic development, and satiety.
Furthermore, we are currently performing a randomized,
double-blinded, crossover, placebo-controlled clinical trial
on supplementation with PA concentrate oil (Clinical-
Trials.gov Identifier: NCT03372733) to investigate its
effect on cardiometabolic biomarkers.
Results: In type II diabetic mouse models that were
orally administered PA for 4 week, PA improved insulin
resistance and lipid profile through regulating lipogenic and
inflammatory genes. In diet-induced atherosclerotic LDLR-
KO mice that were fed Western diet supplemented with PA
concentrate for 12 weeks, dietary PA, but not oleic-rich
olive oil, reduced atherosclerosis. These favorable changes
were was associated with improvement of lipid and glucose
metabolism, and favorable changes in regulatory genes
involved in lipid metabolism and inflammation. Further-
more, oral administration of PA also caused dose-depen-
dently increased satiety in SD rats compared with C16:0 or
C18:1, possibly due to an increase production of satiety
hormones.
Conclusions: In summary, the American Heart Asso-
ciation and Dietary Guidelines for Americans have long
advised the replacement of saturated fatty acids with
unsaturated fatty acids including MUFAs, but a more
detailed understanding on the effect of various types of
dietary MUFAs on CVD risk is needed. Our pre-clinical
trials suggest that enrichment of dietary PA may have
beneficial and perhaps unique effects on CVD risk
factors, and thus could lead to new dietary
e45
recommendations and improvements in the formulation
of MUFA supplements.
317
Effects of Conjugated Linoleic Acid (CLA) on
HDL-C and Triglyceride levels in Subjects
with and without the Metabolic Syndrome: A
Systematic Review and Meta-analysis
Rossana Maria Calderon Moreno, MD,
Ricardo Correa Marquez, MD,
Anna Oberg, MD PhD,
Stefania Papatheodorou, MD, PhD, (New York, NY)
Lead Author’s Financial Disclosures: None.
Study Funding: None.
Background/Synopsis: CLA supplementation has
been widely used by the general population as a weight
reduction agent. In-vitro and animal studies have reported
beneficial metabolic effects including cholesterol and
triglyceride lowering effects, as well as anti-atherogenic
actions potentially via PPARƴ-activation. However, find-
ings in humans have been mixed, with some studies even
reporting harmful effects.
Objective/Purpose: The aim of the present systematic
review and meta-analysis is to evaluate the available
evidence of the effects of CLA on relevant aspects of the
lipoprotein profile in terms of metabolic syndrome, such as
HDL-C and triglyceride levels.
Methods: We conducted a systematic literature search to
identify studies up to December 2017. Only randomized
controlled trials (RCTs) of t10-c12 CLA isomer or mix
50:50 CLA t10-c12 and c9-t11 compared to placebo on
healthy subjects or with components of the metabolic
syndrome were selected. The quality of individual studies
was assessed using the Cochrane’s Risk of Bias tool. When
appropriate, results were pooled to obtain weighted mean
differences (WMDs) with 95% CI. Small study effects were
assessed in funnel plots, and heterogeneity was further
explored in subgroup analysis.
Results: A total of 17 RCTs were included in the
qualitative review, which identified between study dif-
ferences in type of participants, length and dose of
intervention, and study quality. Meta-analysis of 13
studies showed that CLA was associated with a small
reduction in HDL-C levels (-2.06 mg/dL 95%CI -3.74,
-0.39, p50.016) and an increase in triglyceride levels
(7.54 mg/dL, 95% CI 1.20, 13.88, p50.020). Subgroup
analysis indicated that the differences were largely
driven by interventions with higher CLA doses (. 4g/
day). Sensitivity analysis removing studies with high risk
of bias still showed a statistically significant decrease in
HDL-C levels while the effects on triglycerides was no
longer seen.
Conclusions: Our systematic review and meta-analysis
concluded that there is no beneficial effects of CLA on