Diabetes Research and Clinical Practice - Volume 120 - Supplement 1 - October 2016

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upon high fat diet (HFD) feeding. Intriguingly, the expression
of NADPH oxidase genes to produce ROS was alleviated
whereas that of anti-oxidant genes was enhanced in adipose
tissue from HFD-fed G6PD mut mice. In diet-induced obesity
(DIO), adipose tissue of G6PDmut mice decreased expression of
inflammatory cytokines, accompanied with down-regulated
pro-inflammatory macrophages. In accordance with these,
macrophages from G6PDmut mice greatly suppressed LPS-
induced pro-inflammatory signaling cascades, leading to
enhance insulin sensitivity in adipocytes and hepatocytes.
Furthermore, adoptive transfer of G6PD mut bone marrow into
wild type mice attenuated adipose tissue inflammation and
improved glucose tolerance in DIO. Collectively, these data
suggest that down-regulation of macrophage G6PD would
ameliorate insulin resistance in obesity through suppression
of pro-inflammatory responses.
S13-3
Obesity, inflammation and diabetic kidney disease
Chi Ho LEE1. 1University of Hong Kong, Hong Kong
Obesity has become an epidemic, globally. In parallel with this
is a rapid surge in the prevalence of both type 2 diabetes
mellitus and its related complications. Although mortality
from macro-vascular complications like coronary heart
disease and stroke has improved with the advent of potent
statins, the incidence of diabetic kidney disease is still on the
rise and it remains a major cause of end-stage renal failure
worldwide.
Obesity causes dysfunction of adipose tissue, resulting in
chronic inflammation and an imbalance of various adipo-
kines. Over the past decade, the role of inflammation in dia-
betic kidney disease has been increasingly recognized. These
have facilitated not only the improved understanding of the
complex pathogenic mechanisms of diabetic kidney disease,
but also the development of novel therapeutic strategies in
tackling this devastating complication of diabetes.
In this short talk, the association between inflammation and
diabetic kidney disease will be discussed. Furthermore, as
some adipokines or obesity relatedmarkers, such as adipocyte
fatty acid-binding protein and fibroblast growth factor 21, have
been recently investigated as renal biomarkers, their roles as
potential useful candidate markers of diabetic kidney disease
will also be presented.
S13-4
The relationship between obesity and insulin resistance in
Asian patients
E.S. TAI1,2,3. 1Department of Medicine, Yong Loo Lin School of
Medicine, National University of Singapore, 2Cardiovascular and
Metabolic Program, Duke-National University of Singapore Graduate
Medical School, 3Genome Institute of Singapore, Singapore
Obesity and insulin resistance are key pathophysiologic fea-
tures of type 2 diabetes (T2D). Obesity and insulin resistance
are correlated. However, insulin resistance and features of the
metabolic syndrome are manifest a relatively low levels of
body mass index in Asians than they are in populations of
European ancestry. It has been suggested that this relates
to the fact that body mass index under-estimates the degree of
adiposity in Asians. Others have suggested that this relates
to the relatively greater proportion of visceral fat related to
total adiposity in Asians. We have found that the ethnicity
modulates the relationship between obesity and insulin
resistance. In South Asians, insulin resistance is present
even at low body mass index, suggesting that in this ethnic
group, insulin resistance does not require the presence of
obesity. In contrast, while Chinese and Malays are very insulin
sensitive when they are lean, with increasing levels of obesity,
insulin sensitivity rapidly declines so that at a BMI in the
region of 27 –28 kg/m 2, there is no difference between Chinese,
Malays and South Asians in relation to insulin sensitivity. This
suggests that obesity may have a greater impact in Chinese
and Malays than in South Asians. This provides unique
opportunities to dissect out obesity dependent and obesity
independent pathways leading to insulin resistance.
S13-5
17β-hydroxysteroid dehydrogenase-13 is a lipogenic lipid
droplet-associated protein and is regulated by an LXRα-
SREBP1c axis in the liver
Xiao-yan ZHANG1,2, Wen SU2, Bing WANG1, You-fei GUAN1,2.
1Advanced Institute for Medical Sciences, Dalian Medical University,
Dalian, Liaoning 116044, 2Department of Physiology, AstraZeneca –
Shenzhen University Joint Institute of Nephrology, Shenzhen
University Health Science Center, Shenzhen, 518060, China
Nonalcoholic fatty liver disease (NAFLD) is characterized by
a massive accumulation of lipid droplets (LDs). By using 2D
LC-MS/MS, we identified a novel liver-specific lipid droplet-
associated protein, 17β-hydroxysteroid dehydrogenase-13
(17β-HSD13). 17β-HSD13 expression was significantly upregu-
lated in the livers of patients and mice with NAFLD. Increased
hepatic 17β-HSD13 and its LD surface location were confirmed
in type 2 diabetic db/db (diabetic) mice and high-fat diet-fed
mice. Adenovirus-mediated hepatic overexpression of
human 17β-HSD13 induced a fatty liver phenotype in C57BL/
6 mice, with a significant increase in mature sterol regulatory
element-binding protein 1 (SREBP1) and fatty acid synthase
levels. These findings demonstrate that 17β-HSD13 is a
pathogenic protein in the development of NAFLD. To further
characterize the molecular mechanisms involved in the
regulation of 17β-HSD13 gene expression, we determined the
effect of liver X receptors on 17β-HSD13 expression. We found
that treatment with T0901317, a non-specific LXR agonist
for both LXRα and LXRβ, increased both 17β-HSD13 mRNA
and protein levels in cultured hepatocytes. It also significantly
upregulated hepatic 17β -HSD13 expression in wild-type (WT)
and LXRβ−/− mice but not in LXRα−/− mice. Basal expression
of 17β-HSD13 in the livers of LXRα −/− mice was lower than
that in the livers of WT and LXRβ −/− mice. Moreover, induction
of hepatic 17β-HSD13 expression by T0901317 was almost
completely abolished in SREBP-1c−/− mice. Bioinformatics
analysis revealed a consensus sterol regulatory element
(SRE)-binding site in the promoter region of the 17 β-HSD13
gene. A 17 β-HSD13 gene promoter-driven luciferase reporter
and ChIP assays further confirmed that 17β-HSD13 gene was
under direct control of SREBP-1c. Collectively, these findings
demonstrate that 17β -HSD13 is a lipogenic lipid-droplet
protein which expression is regulated by the LXRα-SREBP1c
axis. 17β-HSD13 may represent a potential therapeutic target
for the treatment of NAFLD.
Adipocyte Biology and Insulin
Resistance
S20-1
Lipid dynamics in brown fat-mediated thermogenesis and
energy metabolism
Yu-Hua TSENG1. 1Joslin Diabetes Center and Harvard Medical
School, Boston, MA, USA
Obesity is a pandemic and major contributor to metabolic
disorders. Increased adiposity is the main characteristic of
obesity. In mammals, there are two functionally distinct types
of fat tissue: white adipose tissue (WAT), which is specialized
for energy storage, and brown adipose tissue (BAT), which
dissipates energy for thermogenesis via uncoupling protein 1
(UCP1). In addition to the classical brown adipocytes, UCP1-
positive “beige” or “brite” adipocytes can be recruited within
Speech Abstracts / Diabetes Research and Clinical Practice 120S1 (2016) S1–S39 S22