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. Author manuscript; available in PMC: 2023 Apr 5.
Published in final edited form as: Cell Metab. 2022 Mar 16;34(4):549–563.e8. doi: 10.1016/j.cmet.2022.02.012

Figure 3. Whole-body loss of a single allele and AgRP neuron-specific loss of both alleles of Ptprd is protective against diet-induced obesity in females.

Figure 3.

(a) Weekly body weights of wildtype (Ptprd+/+; n = 16) and heterozygous Ptprd knockout Ptprd+/−; n = 24) female mice maintained on ad libitum normal chow (NC) diet.

(b,c) Cumulative food intake and hourly energy expenditure of 10-week-old Ptprd+/+ and Ptprd+/− female mice on NC over 3 days using the Promethion metabolic system (food intake: Ptprd+/+ n = 8; Ptprd+/− n = 10; Energy expenditure: Ptprd+/− n = 8; Ptprd+/− n = 14).

(d,e) Weekly body weight change of Ptprd+/+ and Ptprd+/− females maintained on high fat diet (HFD) from 5-weeks of age, with food intake measured in a randomly selected cohort of 16-week-old female mice from each group (body weight change: Ptprd+/+ n = 9, Ptprd+/− n = 12; food intake: Ptprd+/+ n = 4; Ptprd+/− n = 4).

(f) Body weight of 6-week-old Ptprdflox/flox and AgRP-cre; Ptprdflox/flox maintained on ad libitum NC diet (Ptprdflox/flox n = 9, AgRP-cre; Ptprdflox/flox n = 10)

(g,h) Cumulative food intake and hourly energy expenditure of 8-week-old Ptprdflox/flox and AgRP-cre; Ptprdflox/flox mice maintained on ad libitum NC over 4 days using the Promethion system (n = 4/group).

(i,j) Weekly body weight change of Ptprdflox/flox (n = 9), AgRP-cre; Ptprdflox/+ (n = 4) and AgRP-cre; Ptprdflox/flox (n = 10) females maintained on high fat diet (HFD) from 5 weeks of age, with food intake measured in 14-week-old females from each group (Ptprdflox/flox :n = 8, AgRP-cre; Ptprdflox/+ : n = 5 and AgRP-cre; Ptprdflox/flox: n = 8).

(k) Schematic figure showing bilateral stereotactic injection of virus (AAV) containing Ptprd sgRNA with AAV expressing mCherry (control) or Cas9 (AgRPPtprd-KO) in the arcuate (ARC) nucleus of adult AgRP-cre female mice.

(l) Body weight of control and AgRPPtprd-KO female mice maintained on NC diet from day 0 to day 48 post stereotactic injection (control: n = 8; AgRPPtprd-KO: n = 11).

(m) Cumulative food intake measured every fourth day of control and AgRPPtprd-KO female mice maintained on NC diet (control: n = 6; AgRPPtprd-KO: n = 11).

(n,o) Body weight change and cumulative food intake of control and AgRPPtprd-KO female mice subjected to HFD on day 48 post stereotactic injection of AAVs coding cas9 and Ptprd sgRNA (control: n = 6-7; AgRPPtprd-KO: n = 11).

*P < 0.05, **P < 0.01, ***P < 0.001 and ****P < 0.0001; by Student’s t-test (e,f,j,l), ‘effect of genotype’ determined by repeated measures two-way ANOVA (a,b,c,g,h) with point-comparison by multiple unpaired t-test (d,i,m,n,o). Circle and square symbol represent mice maintained on NC diet and HFD, respectively. Data are represented as mean ± SEM. See also Figure S5–S7.