Obesity resistance of the stearoyl-CoA desaturase-deficient (<i>scd1</i>
                  <sup>-/-</sup>) mouse results from disruption of the epidermal lipid barrier and adaptive thermoregulation

Binczek, Erika; Jenke, Britta; Holz, Barbara; Günter, Robert Heinz; Thevis, Mario; Stoffel, Wilhelm

doi:10.1515/bc.2007.046

Cited by 80 publications

(79 citation statements)

References 27 publications

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“…Other models with similar heat loss through the skin also may protect against diet-induced obesity (Binczek et al, 2007). Nevertheless, the postprandial clearance of plasma triglycerides was markedly increased in the Apom À/À mice, even when mice were kept at 30 C, which argues against a major effect of the reduced core body temperature on BAT activity.…”

Section: Discussionmentioning

confidence: 96%

The apolipoprotein M/S1P axis controls triglyceride metabolism and brown fat activity

et al. 2018

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ArticleThe Apolipoprotein M/S1P Axis Controls Triglyceride Metabolism and Brown Fat Activity SUMMARYApolipoprotein M (apoM) is the carrier of sphingosine-1-phosphate (S1P) in plasma high-density lipoproteins. S1P is a bioactive lipid interacting with five receptors (S1P 1-5 ). We show that lack of apoM in mice increases the amount of brown adipose tissue (BAT), accelerates the clearance of postprandial triglycerides, and protects against diet-induced obesity (i.e., a phenotype similar to that induced by cold exposure or b 3 -adrenergic stimulation). Moreover, the data suggest that the phenotype of apoM-deficient mice is S1P dependent and reflects diminished S1P 1 stimulation. The results reveal a link between the apoM/S1P axis and energy metabolism.

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Section: Discussionmentioning

confidence: 96%

The apolipoprotein M/S1P axis controls triglyceride metabolism and brown fat activity

et al. 2018

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“…The lipid profile of the skin affects one of its most important functions of serving as a barrier against heat and water loss to the environment (59,60). Mice with a global SCD1 deficiency have severe impairments in the structure of the skin, characterized by sebaceous gland hypoplasia, dry skin, and alopecia (17,18,(61)(62)(63). SCD1-deficient mice also have a hypermetabolic phenotype and have been shown to be resistant to weight gain, despite persistent hyperphagia (4, 6 -8).…”

Section: Discussionmentioning

confidence: 99%

Skin-specific Deletion of Stearoyl-CoA Desaturase-1 Alters Skin Lipid Composition and Protects Mice from High Fat Diet-induced Obesity

Sampath

Flowers

Liu

et al. 2009

Journal of Biological Chemistry

142

199

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Stearoyl-CoA desaturase-1 (SCD1) catalyzes the synthesis of monounsaturated fatty acids and is an important regulator of whole body energy homeostasis. Severe cutaneous changes in mice globally deficient in SCD1 also indicate a role for SCD1 in maintaining skin lipids. We have generated mice with a skinspecific deletion of SCD1 (SKO) and report here that SKO mice display marked sebaceous gland hypoplasia and depletion of sebaceous lipids. In addition, SKO mice have significantly increased energy expenditure and are protected from high fat diet-induced obesity, thereby recapitulating the hypermetabolic phenotype of global SCD1 deficiency. Genes of fat oxidation, lipolysis, and thermogenesis, including uncoupling proteins and peroxisome proliferator-activated receptor-␥ co-activator-1␣, are up-regulated in peripheral tissues of SKO mice. However, unlike mice globally deficient in SCD1, SKO mice have an intact hepatic lipogenic response to acute high carbohydrate feeding. Despite increased basal thermogenesis, SKO mice display severe cold intolerance because of rapid depletion of fuel substrates, including hepatic glycogen, to maintain core body temperature. These data collectively indicate that SKO mice have increased cold perception because of loss of insulating factors in the skin. This results in up-regulation of thermogenic processes for temperature maintenance at the expense of fuel economy, illustrating cross-talk between the skin and peripheral tissues in maintaining energy homeostasis.Obesity is a multifactorial disease stemming from a combination of genetic, dietary, and lifestyle factors and the interaction between these components (1-3). The microsomal enzyme, stearoyl-CoA desaturase-1 (SCD1), 3 is a critical control point in the development of metabolic diseases, including obesity and insulin resistance. SCD1 catalyzes the conversion of saturated fatty acids, such as palmitate (16:0) and stearate (18: 0), into their ⌬-9 monounsaturated products, palmitoleate (16:1 n-7) and oleate (18:1 n-9), respectively. Mice lacking the SCD1 enzyme because of a global deletion of the Scd1 gene (GKO) are lean and protected from diet-induced and leptin deficiency-induced obesity. These mice have a marked increase in energy expenditure and almost complete protection from high fat diet-induced weight gain and glucose intolerance (4 -10). Because SCD1 is expressed in multiple tissues, including liver, brown and white adipose tissue, skeletal muscle, and skin, it has been difficult to determine the relative contributions of these tissues to the dramatically altered metabolic phenotypes of GKO mice. Studies using antisense oligonucleotide-mediated approaches to knock down Scd1 expression have reported protection from diet-induced weight gain and hepatic insulin resistance upon hepatic SCD1 inhibition (11-13). However, whereas the liver is a major target of these antisense oligonucleotides, they have also been reported to affect expression of target genes in adipose tissue (13,14) and possibly other organs (15). Using Cre re...

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“…Hepatic steatosis can develop in a dietary mouse model despite sustained downregulation of SCD1 [43]. In addition, total SCD1 deficiency resulted in a noticeable phenotype with alopecia [44], abnormalities in the epidermal lipid barrier leading to breakdown of thermoregulation and a metabolic wasting syndrome that could in part explain the excessive energy expenditure [45]. Moreover, SCD1-deficient mice on a low-fat, high-carbohydrate diet developed severe hypercholesterolaemia and had a large decrease in HDL-cholesterol levels [27].…”

Section: Discussionmentioning

confidence: 99%

Low hepatic stearoyl-CoA desaturase 1 activity is associated with fatty liver and insulin resistance in obese humans

et al. 2008

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Aims/hypothesis Stearoyl-CoA desaturase 1 (SCD1) is the rate-limiting enzyme in monounsaturated fatty acid synthesis. It is imperative for the assembly of VLDL particles, which transport triacylglycerol (TG) from liver to adipose tissue and other sites. We aimed to determine the role of hepatic SCD1 activity in human glucose and lipid metabolism. Methods We studied 54 people participating in a lifestyle intervention programme with diet modification and increased physical activity. Insulin sensitivity was determined during a euglycaemic-hyperinsulinaemic clamp and estimated from an OGTT. Liver fat was quantified by 1 H-magnetic resonance spectroscopy at baseline and after 9 months of intervention. The pattern of fatty acids in serum VLDL-TGs was determined by ultracentrifugation followed by thin layer and gas chromatography, with the 18:1 n-9: 18:0 ratio providing an index of hepatic SCD1 activity. Results The hepatic SCD1 activity index correlated negatively with liver fat (r=−0.29, p=0.04) and positively with insulin sensitivity, both p=0.003) and clamp-derived (r=0.27, p=0.07). These correlations depended on overall adiposity. They were absent in leaner participants (n=27, liver fat: p=0.34, insulin sensitivity [OGTT]: p=0.75, insulin sensitivity [clamp]: p=0.24), but were strong in obese individuals (n=27, p=0.004, p=0.0002 and p=0.006, respectively). Furthermore, during intervention a high SCD1 activity index at baseline predicted a decrease in liver fat only in obese participants (r=−0.46, p=0.02). Conclusions/interpretation Our data suggest that high hepatic SCD1 activity may regulate fat accumulation in the liver and possibly protects from insulin resistance in obesity.

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Obesity resistance of the stearoyl-CoA desaturase-deficient (scd1 ^-/-) mouse results from disruption of the epidermal lipid barrier and adaptive thermoregulation

Cited by 80 publications

References 27 publications

The apolipoprotein M/S1P axis controls triglyceride metabolism and brown fat activity

The apolipoprotein M/S1P axis controls triglyceride metabolism and brown fat activity

Skin-specific Deletion of Stearoyl-CoA Desaturase-1 Alters Skin Lipid Composition and Protects Mice from High Fat Diet-induced Obesity

Low hepatic stearoyl-CoA desaturase 1 activity is associated with fatty liver and insulin resistance in obese humans

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Obesity resistance of the stearoyl-CoA desaturase-deficient (scd1 -/-) mouse results from disruption of the epidermal lipid barrier and adaptive thermoregulation

Cited by 80 publications

References 27 publications

The apolipoprotein M/S1P axis controls triglyceride metabolism and brown fat activity

The apolipoprotein M/S1P axis controls triglyceride metabolism and brown fat activity

Skin-specific Deletion of Stearoyl-CoA Desaturase-1 Alters Skin Lipid Composition and Protects Mice from High Fat Diet-induced Obesity

Low hepatic stearoyl-CoA desaturase 1 activity is associated with fatty liver and insulin resistance in obese humans

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Obesity resistance of the stearoyl-CoA desaturase-deficient (scd1 ^-/-) mouse results from disruption of the epidermal lipid barrier and adaptive thermoregulation