Intermittent Fasting Aggravates Lupus Nephritis through Increasing Survival and Autophagy of Antibody Secreting Cells in MRL/lpr Mice

Abstract

Systemic lupus erythematosus (SLE) is an autoimmune disease in which the main contributors to organ damage are antibodies against autoantigens, such as double-stranded DNA (dsDNA). Calorie restriction and intermittent fasting (IF) have been shown to improve autoimmune disease symptoms in patients and animal models. Here, we tested the hypothesis that IF might improve symptoms in MRL/lpr mice, which spontaneously develop an SLE-like disease. Groups of mice were fed every other day (IF) or provided food ad libitum (controls), and various lupus-associated clinicopathological parameters were analyzed for up to 28 weeks. Contrary to expectations, anti-dsDNA antibody levels, immune complex deposition in the kidney, and glomerular injury were higher in the IF group than the control group, although there were no differences in spleen and lymph node weights between groups. Proteinuria was also worsened in the IF group. IF also increased the abundance of B cells, plasmablasts, and plasma cells and elevated autophagy in plasma cells in the spleen and lymph nodes. Secretion of anti-dsDNA antibody by splenocytes in vitro was reduced by chloroquine-induced inhibition of autophagy. These results suggest that IF exacerbates lupus nephritis in MRL/lpr mice by increasing autoantibody immune complex formation.

Alternate-Day Fasting Ameliorates Newly Established Sjögren’s Syndrome-like Sialadenitis in Non-Obese Diabetic Mice

“…In addition, ADF did not significantly alter the mRNA level of BAFF, a factor critical for the maturation and survival of B cells in the SMGs, and did not affect the production of antinuclear and anti-M3R autoantibodies, indicating that the protective role of ADF in sialadenitis in NOD mice is not associated with the reduced autoantibody-secreting activities of B cells. Despite the profound and widely reported immunoregulatory effects of intermittent fasting [22][23][24][25][26], one recent study showed that MRL/lpr lupus-prone mice with intermittent fasting exhibited enhanced B cell activity and autoantibody production, and an exacerbated severity of nephritis [31]. The different impacts of intermittent fasting on B cell activity and function are probably attributed to distinct disease contexts, which awaits future investigations.…”

Intermittent Fasting—A Healthy Dietary Pattern for Diabetic Nephropathy

“…The two predominant patterns of IF include: (1) time-restricted feeding, which contains three variants—16/8, 18/6, and 20/4—16/8 consists of a 16 h fast followed by an 8 h eating period, 18/6 consists of fasting for 18 h followed by 6 h eating, and 20/4 consists of fasting for 20 h followed by 4 h eating [ 8 ]; and (2) alternating 24 h fasting with 24 h feeding, and the 5/2 or 4/3 systems, in which one eats for 5 days of the week and fasts for 2 days, or eats for 4 days and fasts for 3 days [ 8 ] ( Figure 1 ). Recently, IF has also been shown to modulate systemic metabolic status through multiple mechanisms, thereby delaying the progression of various diseases, such as cardiovascular [ 9 , 10 ], neurological [ 11 , 12 ], and autoimmune [ 13 , 14 , 15 ] diseases. The role of IF in diabetic nephropathy (DN), a metabolic disorder, is now being investigated in depth.…”