Dataset Information

Altered Body Weight Regulation in CK1? Null and tau Mutant Mice on Regular Chow and High Fat Diets.

ABSTRACT: Disruption of circadian rhythms results in metabolic dysfunction. Casein kinase 1 epsilon (CK1?) is a canonical circadian clock gene. Null and tau mutations in CK1? show distinct effects on circadian period. To investigate the role of CK1? in body weight regulation under both regular chow (RC) and high fat (HF) diet conditions, we examined body weight on both RC and HF diets in CK1? (-/-) and CK1? (tau/tau) mice on a standard 24?hr light-dark (LD) cycle. Given the abnormal entrainment of CK1? (tau/tau) mice on a 24?hr LD cycle, a separate set of CK1? (tau/tau) mice were tested under both diet conditions on a 20?hr LD cycle, which more closely matches their endogenous period length. On the RC diet, both CK1? (-/-) and CK1? (tau/tau) mutants on a 24?hr LD cycle and CK1? (tau/tau) mice on a 20?hr LD cycle exhibited significantly lower body weights, despite similar overall food intake and activity levels. On the HF diet, CK1? (tau/tau) mice on a 20?hr LD cycle were protected against the development of HF diet-induced excess weight gain. These results provide additional evidence supporting a link between circadian rhythms and energy regulation at the genetic level, particularly highlighting CK1? involved in the integration of circadian biology and metabolic physiology.

SUBMITTER: Zhou L

PROVIDER: S-EPMC4837286 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Altered Body Weight Regulation in CK1ε Null and tau Mutant Mice on Regular Chow and High Fat Diets.

Zhou Lili L Summa Keith C KC Olker Christopher C Vitaterna Martha H MH Turek Fred W FW

Genetics research international 20160406

Disruption of circadian rhythms results in metabolic dysfunction. Casein kinase 1 epsilon (CK1ε) is a canonical circadian clock gene. Null and tau mutations in CK1ε show distinct effects on circadian period. To investigate the role of CK1ε in body weight regulation under both regular chow (RC) and high fat (HF) diet conditions, we examined body weight on both RC and HF diets in CK1ε (-/-) and CK1ε (tau/tau) mice on a standard 24 hr light-dark (LD) cycle. Given the abnormal entrainment of CK1ε (t ...[more]

PMID: 27144030

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Project description:BackgroundObesity is a leading risk factor for osteoarthritis (OA). In contrast, calorie restriction (CR) may lessen OA due to improved systemic inflammatory status and reduced weight-bearing. The aim of this study was to determine how CR with regular chow versus a high-fat diet (HFD) alters OA progression using the Hartley guinea pig model of disease.MethodsTwenty-four male guinea pigs were allocated to four groups at 2 months of age: (1) ad libitum regular chow (obese), (2) CR regular chow (lean), (3) ad libitum HFD, and (4) CR HFD. Animals in both HFD groups ate identical amounts and were combined into one HFD group for analyses. At 5 months, hind limbs were harvested for microcomputed tomography (microCT) and histopathologic evaluation of knee OA. Total body, gonad fat, and infrapatellar fat pad (IFP) masses were recorded. IFPs were collected for gene expression analysis. Immunohistochemistry for monocyte chemoattractant protein-1 (MCP-1) was performed on intact joints. Serum was utilized for protein C3 measurement. All data were compared using ordinary one-way ANOVA analyses with Tukey's post-hoc tests.ResultsBody mass in the lean and HFD groups were similar and lower than the obese group. Despite this, gonad fat pads in the HFD group were comparable to the obese group. MicroCT and histologic OA scores were similar in obese and HFD groups; both scores were significantly lower in the lean group. Obese and HFD groups displayed increased gene expression of pro-inflammatory and catabolic mediators in IFPs relative to lean animals. Consistent with this, immunohistochemistry for MCP-1 in knee joints demonstrated strong positive staining in obese and HFD groups but was minimally detected in lean animals. Serum protein C3 levels were also statistically higher.ConclusionsThis study demonstrated that CR with a regular chow diet lessened knee OA in the Hartley guinea pig and was associated with decreased local and systemic inflammation compared to obese animals. HFD animals, although under CR conditions, had OA scores and inflammatory markers similar to obese animals. Thus, diet composition, and not solely body weight, may be a key factor in development of OA.

Dataset Information

Altered Body Weight Regulation in CK1? Null and tau Mutant Mice on Regular Chow and High Fat Diets.

Publications

Altered Body Weight Regulation in CK1ε Null and tau Mutant Mice on Regular Chow and High Fat Diets.

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