title: Loss of SFRP4 Alters Body Size, Food Intake, and Energy Expenditure in Diet-Induced Obese Male Mice.
abstract: Secreted frizzled-related protein 4 (SFRP4) is an extracellular regulator of the wingless-type mouse mammary tumor virus integration site family (WNT) pathway. SFRP4 has been implicated in adipocyte dysfunction, obesity, insulin resistance, and impaired insulin secretion in patients with type 2 diabetes. However, the exact role of SFRP4 in regulating whole-body metabolism and glucose homeostasis is unknown. We show here that male Sfrp4(-/-) mice have increased spine length and gain more weight when fed a high-fat diet. The body composition and body mass per spine length of diet-induced obese Sfrp4(-/-) mice is similar to wild-type littermates, suggesting that the increase in body weight can be accounted for by their longer body size. The diet-induced obese Sfrp4(-/-) mice have reduced energy expenditure, food intake, and bone mineral density. Sfrp4(-/-) mice have normal glucose and insulin tolerance and β-cell mass. Diet-induced obese Sfrp4(-/-) and control mice show similar impairments of glucose tolerance and a 5-fold compensatory expansion of their β-cell mass. In summary, our data suggest that loss of SFRP4 alters body length and bone mineral density as well as energy expenditure and food intake. However, SFRP4 does not control glucose homeostasis and β-cell mass in mice.
authors.affiliation: Regeneron Pharmaceuticals, Inc, Tarrytown, New York 10591.
authors.forename: Jason
authors.initials: J
authors.lastname: Mastaitis
authors.affiliation: Regeneron Pharmaceuticals, Inc, Tarrytown, New York 10591.
authors.forename: Mark
authors.initials: M
authors.lastname: Eckersdorff
authors.affiliation: Regeneron Pharmaceuticals, Inc, Tarrytown, New York 10591.
authors.forename: Soo
authors.initials: S
authors.lastname: Min
authors.affiliation: Regeneron Pharmaceuticals, Inc, Tarrytown, New York 10591.
authors.forename: Yurong
authors.initials: Y
authors.lastname: Xin
authors.affiliation: Regeneron Pharmaceuticals, Inc, Tarrytown, New York 10591.
authors.forename: Katie
authors.initials: K
authors.lastname: Cavino
authors.affiliation: Regeneron Pharmaceuticals, Inc, Tarrytown, New York 10591.
authors.forename: Johnpaul
authors.initials: J
authors.lastname: Aglione
authors.affiliation: Regeneron Pharmaceuticals, Inc, Tarrytown, New York 10591.
authors.forename: Haruka
authors.initials: H
authors.lastname: Okamoto
authors.affiliation: Regeneron Pharmaceuticals, Inc, Tarrytown, New York 10591.
authors.forename: Erqian
authors.initials: E
authors.lastname: Na
authors.affiliation: Regeneron Pharmaceuticals, Inc, Tarrytown, New York 10591.
authors.forename: Trevor
authors.initials: T
authors.lastname: Stitt
authors.affiliation: Regeneron Pharmaceuticals, Inc, Tarrytown, New York 10591.
authors.forename: Melissa G
authors.initials: MG
authors.lastname: Dominguez
authors.affiliation: Regeneron Pharmaceuticals, Inc, Tarrytown, New York 10591.
authors.forename: Jennifer P
authors.initials: JP
authors.lastname: Schmahl
authors.affiliation: Regeneron Pharmaceuticals, Inc, Tarrytown, New York 10591.
authors.forename: Calvin
authors.initials: C
authors.lastname: Lin
authors.affiliation: Regeneron Pharmaceuticals, Inc, Tarrytown, New York 10591.
authors.forename: Nicholas W
authors.initials: NW
authors.lastname: Gale
authors.affiliation: Regeneron Pharmaceuticals, Inc, Tarrytown, New York 10591.
authors.forename: David M
authors.initials: DM
authors.lastname: Valenzuela
authors.affiliation: Regeneron Pharmaceuticals, Inc, Tarrytown, New York 10591.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Murphy
authors.affiliation: Regeneron Pharmaceuticals, Inc, Tarrytown, New York 10591.
authors.forename: George D
authors.initials: GD
authors.lastname: Yancopoulos
authors.affiliation: Regeneron Pharmaceuticals, Inc, Tarrytown, New York 10591.
authors.forename: Jesper
authors.initials: J
authors.lastname: Gromada
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001823:Body Composition / Q000235:genetics; D049628:Body Size / Q000235:genetics*; D015519:Bone Density / Q000235:genetics*; D059305:Diet, High-Fat; D004435:Eating / Q000235:genetics*; D004734:Energy Metabolism / Q000235:genetics*; D005247:Feeding Behavior; D055879:Gene Knock-In Techniques; D005951:Glucose Tolerance Test; D057809:HEK293 Cells; D006706:Homeostasis / Q000235:genetics; D006801:Humans; D007328:Insulin / Q000378:metabolism; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009765:Obesity; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D060449:Wnt Signaling Pathway; D055114:X-Ray Microtomography; D000094742:Secreted Frizzled-Related Proteins
chemical_list: D001786:Blood Glucose; D007328:Insulin; D011518:Proto-Oncogene Proteins; C498454:Sfrp4 protein, mouse; D000094742:Secreted Frizzled-Related Proteins